Eurofins Discovery
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For more than 40 years, Eurofins Discovery has been a trusted CRO supporting global Drug Discovery clients from Target ID through to Candidate Selection. We offer a complete, single-source solution for drug discovery products and services and are rooted in the deep expertise and best-in-class offerings of 6 premier CROs: Cerep, DiscoverX, EMP Millipore Drug Discovery Solutions, Panlabs, Eurofins Integrated Discovery Ltd UK, and Villapharma. Eurofins Discovery, in partnership with Pharmacology Discovery Services for in vivo services, offers a comprehensive package of drug discovery products and services, including in vitro assays, cell-based phenotypic assays, safety & efficacy, ADME-Tox, chemistry and custom proteins, assay development and in vivo services. We are here to help our clients rapidly advance their drug candidates to the clinic.
The Endocrine Disruption Profile is specifically designed to rapidly and cost-effectively assess the endocrine disrupting potential of chemicals compounds or ingredients in the early stage of their development by measuring in vitro their interactions with targets known to be involved in endocrine disruption effects. Our Endocrine Disruption panel comprises 14 early-stage target-based screening assays corresponding to these molecular initiating events and adverse outcome pathways outlined in the OECD and EPA guidelines. Data delivery turnaround time 15 business days.
Programmed Death-Ligand 2 (PD-L2) Assays
Programmed Death-Ligand 2 (PD-L2) Assays
Propidium Iodide FACS Analysis
Radiochemical Synthesis
Selectivity Profiling
Repetitive Maximum Tolerated Dose (MTD) Rat Study
Repeat Dose Toxicity Study - Rat
Repeat Dose Toxicity Study - Mouse
Spontaneous Metastatic Models
Stable Isotope Synthesis is also available
Streptozotocin Mouse
Streptozotocin Rats
Systemic Lupus Erythematosus Models
Radius Cell Migration Assay available
The central nervous system (CNS) is prone to many diseases and pain-related disorders, especially prevalent during aging. The importance of CNS disorders is indicated by the severity of many of the diseases associated with it. These diseases include depression, epilepsy, psychosis, multiple sclerosis, and many other common, yet difficult-to-treat diseases. Eurofins, through the expertise of Panlabs, has been conducting in vivo testing for CNS and pain disorders for both efficacy and side-effect profiling for over 25 years.
We have applied our in vivo and neuroscience acumen to develop the most relevant CNS and pain-related models including epilepsy, affective disorders, neuroleptic, and multiple sclerosis, acute, inflammatory and neuropathic pain. We also offer translational models of pain such as osteoarthritis and bone cancer pain, a testament to our superlative skills. Additionally, we offer several pain-associated behavioral measurements such as mechanical allodynia, thermal and mechanical hyperalgesia, as well as cold allodynia.
With our ever-expanding portfolio of in vivo models, Eurofins has the necessary skills and expertise to assist you to evaluate whether your candidates are ready for clinical trials.
Advantages of Eurofins for preclinical CNS and pain studies:
50 CNS and pain assay models available
Eurofins has built its reputation as a comprehensive, all-in-one provider of discovery assays to take your project from library to preclinical candidate. While we have worked diligently to ensure our assay catalog has everything necessary to support your drug discovery program, we also understand that standard off-the-shelf assays may not have the parameters you require.
Fortunately, Eurofins is able to provide custom assays by modifying existing assays and creating new assays that are tailored to your needs. Our dedicated scientists, who have developed thousands of binding, enzymatic, cell based and in vivo assays, are always available to help work through your assay design and provide a step-by-step plan for your experiment. By trusting Eurofins with your custom assay needs, you're ensuring your project has the greatest chance for success.
Some of the available platforms to design your custom assays around:
High Content Imaging
MD ImageXpress® Micro
Electrophysiology platforms
IonFlux™ HT
Mass spectrometers
Agilent RapidFire 365
Plate readers
FLIPRTETRA® plus ICCD system
Perkin Elmer EnVision®
BMG PHERAStar® FS
Multiplex immunoassays
MSD® Sector® Imager
Scintillation counting
PerkinElmer 1450 MicroBeta® TriLux
Automation and liquid handling
Labcyte Echo®
Biomek® FXP / NX
Agilent BioCel 1200
Cell preparation
MaxCyte® STX®
Vi-CELL®
Determine your drug’s similarity to existing drugs with BioPrint®
BioPrint® is a large, homogenous pharmacology and ADME database, which provides a unique resource for supporting the drug discovery decision-making process. The database is composed of three main data sets:
Chemical descriptors (structures and chemical information, 2D- and 3D- descriptors)
In vitro data
Collected and curated in vivo effects of drugs
Our standard BioPrint® profile includes the assays used to explore the properties of >2,500 BioPrint® compounds (consisting of marketed drugs and reference compounds), which establishes individual Pharma-ADME fingerprints for each compound.
BioPrint® positions a new drug candidate in the context of marketed drugs, allowing you to anticipate potential in vivo liabilities, predicting off-target activities, and ADME characteristics (drug profile interpretation). BioPrint® can also help identify secondary therapeutic targets that are not genetically related to a test target (target profile design) for drug repositioning.
Advantages of a BioPrint® profile:
Predict in vivo activity from in vitro data
The Foresight™ similarity analysis service allows you to compare your compound's assay results against the assay results of a large reference set of pharmacologically active compounds. The reference set includes marketed drugs, failed development candidates and reference compounds that have well-characterized activities and have been tested against a series of expert-selected hit and lead screening assays. This service is compound-centric and includes all data generated for your compound.
Using the actual data derived from tests run on your compounds, we determine the five compounds in the reference set with the highest similarity score. The score is computed based on the mathematical correlation of assay test results of your compound to the reference set compound assay results, providing you with an insight into potential in vivo activity.
Advantages of a Foresight™ Profile:
The exact mechanisms of a disease can often be poorly understood. When there is little understanding of the disease pathology, in vitro phenotypic assays may provide more insight than target-based screening alone. Phenotypic screening allows researchers to identify new chemical entities and biomarkers without prior knowledge, or bias, of the target(s) underlying the response. Equally important, phenotypic assays provide a systems-based approach to assess compound liability.
Our high content imaging expertise enables the detection of robust phenotypic responses and is a powerful orthogonal approach to target-based screening. With a diverse portfolio consisting of our OncoPanel™, ImmunoSignal™ and functional toxicity service platforms, Eurofins provides you with the phenotypic results you're looking for.
Develop difficult targets and orthologs to meet your drug discovery needs
Outsourcing your stable cell line development to Eurofins will enable you to free up necessary resources while guaranteeing the success your drug development program needs. We have successfully developed hundreds of human GPCR and ion channel stable cell lines and related orthologs, bringing time-tested experience to the table. Our stable cell line development FlexLab option allows you to choose from CHO, HEK, or our proprietary Chem-1 host, a rat hematopoietic, adherent cell line or provide your own.
Our experienced scientists use our proprietary expression vectors to generate cells producing the most functionally active recombinant proteins. Our milestone driven projects give you the flexibility to take projects from proof of concept transient transfections, to selected polyclonal cells and all the way to stability tested monoclonal cell lines.
Advantages of Eurofins' Custom Cell Line Development:
If your intent is to use protein for enzymatic assays, as substrates in biophysical assays (e.g., surface plasmon resonance (SPR)), for crystallography or nuclear magnetic resonance (NMR), we can produce the proteins with the specifications that match your application. Our protein expression experts share a wealth of experience in recombinant protein expression and have produced >400 protein products, all of which are made to demanding control parameters (typically including: ≥ 80% protein purity, ≥ 0.5 mg/L yield, and specified activity for protein kinases).
We have a robust manufacturing process that is highly controlled and documented at every stage with a manufacturing batch record. As a milestone, we can produce a batch of pilot scale material for your in-house testing before you commit to a large scale project.
Our custom protein production and purification skills are unmatched and can be applied to suit your unique needs. We offer bulk manufacturing as well as wild type, mutant, and ortholog proteins. Contact us today to speak with our protein specialists.
Protein expression and purification capabilities:
Toxicity testing is mandated by regulatory agencies for IND submission and is typically performed during the preclinical phase of discovery. However, uncovering toxicity at such a late stage means that considerable investment and time has been lost, jeopardizing the project. Eurofins has developed a reliable high-throughput model of multiplexed toxicity testing which provides a quick and cost-effective option suitable for early liability assessment, when changing lead series has minimum impact on the project. By utilizing imaging expertise with five human primary cell lines, we can provide a sensitive in vitro cell-based method to aid in lead selection and optimization by identifying potential tissue-relevant toxicity earlier in the drug development process.
Our organ toxicity services employ primary cells derived from human donor tissue that are purified and cryopreserved. Primary cells such as the Normal Human Dermal Fibroblasts (NHDF), Human Renal Proximal Tubular Epithelial Cells (HRPTEpiC), Human Umbilical Vein Endothelial Cells (HUVEC) and Human Umbilical Mesenchymal Stem Cells (HUMSC) included in this panel are able to propagate in for a short number of passages before they stop dividing. These cells are banked at a low passage number and proliferate in culture pre- and post-plating. The Human Primary Hepatocytes (HPH) are plated directly from thawed cryovials and do not proliferate in culture.
Our assays employ high-resolution cell imaging to provide more sensitive detection of cell viability determined by proliferation inhibition or cell loss. Our services can be run with a single cell type, the pre-validated primary cell panel, or cell lines chosen through collaboration with our expert scientists who have experience running cytotoxicity assays with hundreds of human cell lines.
Advantages of Eurofins' Organ-Toxicity in Human Primary Cell Panel:
Eurofins Metabolic and Endocrine Models
With today's high caloric diets and sedimentary life style, increasing attention has been focused on remedying associated metabolic disorders, naming obesity and diabetes. In early stages, these issues manifest in metabolic syndrome, a complex disease which is characterized by obesity, insulin resistance, pre-diabetic fasting glucose levels, fatty liver, and low HDL cholesterol levels. Left untreated, metabolic disorders can greatly increase the risk of stroke, type II diabetes, and cardiovascular disease.
Eurofins offers a complete list of qualified models for metabolic disorder, including Type I (induction by streptotozocin) and Type II diabetes models. The type I models allow examination of agents acting on insulin-independent pathways and affording end organ protection from diabetes, while the Type II models are conventional wildtype or genetic variants (db/db, ob/ob or ZDF) used with or without modified test diets to explore the impact of pharmacological agents on glucose metabolism and/or obesity. Diabetic complications in humans include organ-specific microvascular damage with sequelae such as nephropathy, and we offer a panel of chronic kidney disease models, as well as models of acute and chronic hepatic injury.
We are able to expertly provide outcome measure of glucose tolerance or insulin tolerance test, as well as plasma lipid profile and measurements of serum insulin, glucagon, leptin, adiponectin, free fatty acid, cytokines, and other relevant biomarkers. Our in vivo testing expertise can help bring your drug from the discovery phase all the way to clinical trials.
Advantages of preclinical metabolic and endocrine studies with Eurofins:
40 therapeutically relevant models, including:
Transporters are membrane proteins that control the influx and efflux of essential nutrients, ions, neurotransmitters, cellular waste, environmental toxins, and other xenobiotics such as drugs. Drug transporters are composed of two major super families: ABC (ATP binding cassette) and SLC (solute carrier) transporters.
ABC transporters mediate unidirectional efflux and are primarily active transporters as they directly rely on ATP hydrolysis to pump their substrates across membranes. They play major roles in hepatobiliary and urinary excretion of drugs from the blood to the lumen, intestinal absorption of drugs, and in brain blood barrier penetration of drugs.
SLC transporters mediate either drug uptake or efflux and can be facilitated transporters or secondary active transporters, which transport drugs using energy produced by transmembrane movement of other solutes in accordance with their concentration gradient. They play major roles in hepatic and renal uptake, and urinary excretion. Some SLC transporters, such as those for neurotransmitters, are also important drug targets themselves with clinical drugs treating various psychiatric disorders.
Transporters play a significant role in a drug's clinical efficacy and safety. Eurofins, through the expertise of Cerep and Panlabs, has developed robust transporter uptake and inhibition assays to allow quick and cost-effective screening of new molecular entities (NMEs) for their interactions with these transporters.
Advantages of transporter screening with Eurofins:
Eurofins Metabolic and Endocrine Models
With today's high caloric diets and sedimentary life style, increasing attention has been focused on remedying associated metabolic disorders, naming obesity and diabetes. In early stages, these issues manifest in metabolic syndrome, a complex disease which is characterized by obesity, insulin resistance, pre-diabetic fasting glucose levels, fatty liver, and low HDL cholesterol levels. Left untreated, metabolic disorders can greatly increase the risk of stroke, type II diabetes, and cardiovascular disease.
Eurofins offers a complete list of qualified models for metabolic disorder, including Type I (induction by streptotozocin) and Type II diabetes models. The type I models allow examination of agents acting on insulin-independent pathways and affording end organ protection from diabetes, while the Type II models are conventional wildtype or genetic variants (db/db, ob/ob or ZDF) used with or without modified test diets to explore the impact of pharmacological agents on glucose metabolism and/or obesity. Diabetic complications in humans include organ-specific microvascular damage with sequelae such as nephropathy, and we offer a panel of chronic kidney disease models, as well as models of acute and chronic hepatic injury.
We are able to expertly provide outcome measure of glucose tolerance or insulin tolerance test, as well as plasma lipid profile and measurements of serum insulin, glucagon, leptin, adiponectin, free fatty acid, cytokines, and other relevant biomarkers. Our in vivo testing expertise can help bring your drug from the discovery phase all the way to clinical trials.
Advantages of preclinical metabolic and endocrine studies with Eurofins:
40 therapeutically relevant models, including:
Epigenetics, an increasingly popular field of drug discovery, is the study of heritable changes in gene expression that occur without changes in the DNA sequence. The epigenome is considered to be in constant flux and is responsive to environmental and pharmaceutically active molecules. Epigenetics-related enzymes and proteins catalyze the addition or removal of an array of covalent modifications on histone and non-histone proteins. For these reasons, epigenetics is becoming an increasingly important realm for drug therapies. Indeed, several drugs directed towards epigenetic modifying enzymes are already on the market with more in the clinic to treat cancer.
In 2012, ahead of all other CROs, Eurofins recognized the industry's upcoming need for a comprehensive epigenetics program containing all major families. To meet this growing need, we began to develop a range of target based assays using biologically relevant substrates (nucleosomes, histones, and peptides) to create the most meaningful assays. The majority of our proteins/substrates are produced in-house to ensure the highest quality of proteins resulting in high batch to batch reproducibility.
Eurofins' epigenetic toolbox is based on several technology platforms and allows for your choice of technology and/or substrates, providing added flexibility to meet all of your drug discovery needs.
Advantages of Eurofins' Epigenetics Program:
50 Writers, including: SMMT, Kinases, DNMT, HMT and HAT
40 Erasers, including: Demethylases, HDAC / sirtuin and DUB
45 Readers, including: Bromodomain and Methyl readers
17 Off-target and cell-based assays, including acetylation and methylation studies
Gastrointestinal (GI) disease is characterized by abnormalities in the gastrointestinal tract which includes the esophagus, liver, gallbladder, stomach, pancreas, intestines and colon. Inflammation in these areas can cause a variety of GI diseases or dysfunctions and can be difficult to diagnose. According to the CDC, in the United States alone, inflammatory bowel disease (Crohn's disease or ulcerative colitis) affects over 1 million people. Eurofins, through the expertise of Panlabs, has been conducting in vivo testing for both side-effect profiling and efficacy in GI disease for over 25 years.
Our models allow examination of GI motility and colonic function or to test agents designed to prevent a variety of GI related diseases. We also employ a broad range of outcome measures to assess GI safety and/or therapeutic efficacy of novel test articles. By providing the best models, Eurofins looks to be your partner of choice in helping you to discover the next exciting treatment for gastrointestinal disease.
Advantages of preclinical GI studies with Eurofins:
Xenograft and syngeneic and in vivo tumor models
With over 25 years in the industry, Eurofins has refined our skills to excel at providing syngeneic and human tumor xenograft models. Our experience is unparalleled in providing in vivo models of efficacy in murine or human hematologic or carcinoma malignancies.
Our oncology services also feature custom model development for clients' target-specific cell lines as orthotopic, disseminated/metastatic or subcutaneous xenografts, using any of the 300 cell lines from our cell based phenotypic assays found in our OncoPanel™ services. Our ability to establish custom xenograft models from patient-derived tissue is a testament to our skills and experience in oncology services.
Trusting Eurofins with your preclinical oncology studies helps you understand your candidates' efficacy, so you can be confident entering clinical development.
Advantages of profiling with in vivo oncology models:
Understanding the absorption, distribution, metabolism, excretion (ADME) and toxicity (Tox) properties of your compounds is critical in the drug discovery process and can be evaluated by a series of in vitro assays and in vivo studies.
There is a significant advantage to obtaining in vitro ADME data as early as possible in the drug discovery process. For example, hepatic metabolism is a primary determinant of pharmacokinetic behavior and rapid first-pass metabolism is a major cause of low bioavailability. In vitro ADME results serve as good indicators as to whether a compound will be bioavailable, thus these results can assist to eliminate problematic compounds early in discovery and be a useful guide for later stage studies.
Drug toxicity is often the major reason for the withdrawal of an approved drug from the market, with hepatic toxicity and cardiac toxicity being the top two most frequent reasons. While formal toxicity testing is traditionally completed during a late preclinical phase, it has become obvious that a failure at this stage results in significant setbacks and economic loss.
Our assays are designed with the intent to meet regulatory requirements and are suitable for evaluating ADME-Tox properties early in the drug discovery process. With Eurofins cost-effective ADME-Tox assays, we help our clients to eliminate failures earlier in the drug discovery process while liberating them from having to invest internal time and capital to conduct these studies themselves.
ADME-Tox assays available from Eurofins:
Eurofins has the experience and skills needed to bring you early stage pharmacokinetic (PK), oral bioavailability and blood-brain barrier (BBB) data to evaluate your new molecular entity. PK and BBB studies are prerequisite for interpreting preclinical efficacy and toxicology results. Using qualitative measurements of drug exposure, we can provide a solid interpretation of preclinical efficacy. PK data can also help in species selection and design of preclinical toxicology studies.
Eurofins will work with you to understand the physicochemical properties of your test material to develop a dosing and sample collection strategy that will provide you with the most meaningful data. We can obtain blood and/or tissue (e.g. brain) samples following dose administration (IV, PO, IP, IM, SC, IN, and ICV, also short- or long-term continuous infusions) and both serial sampling for PK and parallel sampling for PK, BBB or combined PK-BBB are available. PK/PD studies can be combined using our broad portfolio of pharmacodynamics models.
PK/BBB dosing and sampling studies can be paired with standard or custom bioanalytical methods to provide a concentration versus time curves to provide a complete pharmacokinetic profile for your compound.
Advantages of in vivo pharmacokinetic and blood/brain barrier studies with Eurofins:
Extensive experience with multiple routes of administration, including long-term continuous infusion
Proficient in performing PK and BBB studies
Combined PK/BBB sampling and bioanalytical studies
Renal and biliary clearance
Experience you can trust: >25 years running in vivo preclinical services with a staff averaging 15 years of experience
Long range of efficacy and toxicity studies can be conducted at the same provider
Safety related issues and drug toxicity is a major reason why promising leads don't advance and candidates fail curing clinical development. The 'fail early' mantra in drug discovery was born out of the reality that late-stage failures result in significant setbacks and economic loss.
For early safety and toxicity assessment, Eurofins is the go-to-provider with over 35 years of in vivo safety and early toxicity testing. Combined with our in vitro pharmacology and cell based in vitro toxicity assays services, our in vivo safety services can provide a comprehensive risk profile for your leads at a stage when changes can still be made without a major impact to your project.
We offer a complete list of qualified safety related in vivo models to detect the most commonly observed adverse events in CNS, cardiovascular, respiratory, renal, metabolic, and gastrointestinal functions using a broad panel of industry-standard outcome measures to build a toxicokinetic (TK) profile. We can also provide specialized models, such as our emesis model, to address specific project needs.
Advantages of early, non-GLP safety screening with Eurofins:
Approval and registration of drugs requires a comprehensive assessment of their genotoxic potential. Genotoxicity testing is an integral component of regulatory toxicity evaluation in most countries. Since no single test is capable of detecting all relevant genotoxic end-points, a battery of in vitro and in vivo tests for genotoxicity is recommended by regulatory agencies. The recommended standard test battery includes in vitro tests for gene mutation in bacteria (Ames test) and in mammalian cells (mouse lymphoma assay) or an in vitro test for chromosomal damage in mammalian cells (in vitro micronucleus test or in vitro metaphase chromosomal aberration assay). Additionally, an in vivo test for chromosomal damage (in vivo micronucleus or in vivo chromosomal aberration assay) is required by regulatory agencies as part of an IND application.
Recently, assessment of genotoxicity testing has evolved towards earlier stages of drug discovery in order to identify genotoxic liabilities at a time when changing lead series will have a relatively low impact on a project's timeline and cost. Assays such as the Ames fluctuation test and the in vitro micronucleus assay (for the assessment of the in vitro chromosomal aberration) offered by Eurofins are routinely used for screening compounds.
Advantages of Eurofins' Genotoxicity Assays:
Custom assays to support your drug discovery project
Eurofins has built its reputation as a comprehensive, all-in-one provider of discovery assays to take your project from library to preclinical candidate. While we have worked diligently to ensure our assay catalog has everything necessary to support your drug discovery program, we also understand that standard off-the-shelf assays may not have the parameters you require.
Fortunately, Eurofins is able to provide custom assays by modifying existing assays and creating new assays that are tailored to your needs. Our dedicated scientists, who have developed thousands of binding, enzymatic, cell based and in vivo assays, are always available to help work through your assay design and provide a step-by-step plan for your experiment. By trusting Eurofins with your custom assay needs, you're ensuring your project has the greatest chance for success.
Some of the available platforms to design your custom assays around:
Neuropathic pain models:
Chemotherapy-induced, (Rat)
Spinal Nerve Ligation, (Chung Model, Mouse & Rat)
Chronic Constriction Injury / Sciatic Nerve Ligation, (Bennett Model, Rat)
STZ-induced Diabetes, (Rat)
MIA-induced osteoarthritis pain
Sciatic Nerve Crush Injury
Establish the metabolic profile of a promising compound early in the drug-discovery process
Metabolic profiling of therapeutic compounds at early stages in the drug discovery process is of increasing importance. Drugs that undergo metabolism in vivo may produce pharmacologically active or chemically reactive metabolites which can produce unexpected effects or potential toxicities. The recent FDA Guidance for Industry on Safety Testing of Drug Metabolites1 highlights the relevance of in vitro metabolite profiling early in drug development, as metabolites which are unique to or disproportionate in humans may require additional toxicological studies.
In addition to an extensive panel of in vitro metabolism screening assays, Eurofins is able to perform studies to thoroughly characterize the metabolic products of a drug compound in vivo or in vitro and compare metabolic profiles across species. The key element in metabolite identification studies is the use of state-of the art mass spectrometry instrumentation for sensitive and accurate detection of metabolic products and software tools to efficiently process the complex datasets that are produced from these analyses.
Eurofins employs a Waters Xevo G2 QTOF MS system combined with Acquity UPLC separation to provide high mass accuracy and excellent sensitivity in full scan MS and MS/MS modes. The acquisition method on the Xevo collects precursor and product ion data in two distinct but parallel acquisition functions via rapid switching, so that complete metabolite identification data can be obtained from a single LC injection. If necessary, follow-up selected reaction monitoring or product ion or neutral loss scans can be performed on a triple-quadrupole MS system in order to obtain corroborating data for putative metabolites.
By partnering with Eurofins, you'll be able to better understand your drug candidate's metabolism and stability and obtain a more comprehensive assessment of that compound's metabolic profile.
Flexible options to meet your research needs
Metabolism data on test compounds can be obtained through a choice of experiments, depending on the level of data depth and interpretation required:
Rat MIA (Monoiodoacetate) Models available
Proteases are a class of enzymes which perform proteolysis, the mechanism of digesting or cleaving long chain proteins into smaller fragments by severing the peptide bonds that hold them together. Trypsin, a serine protease secreted by the pancreas, is commonly used in cell tissue culture to cleave the bonds that cells use to adhere to a flask.
Proteases also play a major role in disease. HIV-1 protease is essential to the viral replication process. MMP-9, a matrix metallopeptidase, plays a role in angiogenesis and is a therapeutic target for cancer. Because of their significance in the pathology of disease, proteases are a relevant drug target class.
Our broad portfolio of over 50 proteases spanning across the serine, cysteine, aspartic, and metalloprotease families was designed with you in mind to facilitate your drug discovery process and provide you with the answers you need.
Over 50 targets to support your research, including these families and targets:
The ImmunoSignal™ platform provides a suite of services to understand the immune response to your therapeutic. Our in vitro solutions for discovery pharmacology and preclinical research include multiplexed cytokine analysis and flow cytometry techniques, allowing simultaneous monitoring of pro- and anti-inflammatory markers.
We conduct assays using a unique bank of Peripheral Blood Mononuclear Cells (PBMCs) from donors of diverse ethnical backgrounds, offering genetic diversity. These primary cell banks are from single human donors for a consistent cellular source for cytokine secretion assyes, which is useful for maintaining cross data integrity. Monocytes, T-cells and B-cells have also been isolated from these banks for proliferation and cytokine studies.
Enjoy tailored made solutions for your immunological studies by using our custom services. We can use your specified cell lines or sub-cellular components isolated from white blood cells or design a panel to meet your specific needs.
Whether you decide on an off-the-shelf solution or a highly customized assay, Eurofins has the immunology solution you need to further your drug development program.
Advantage of ImmunoSignal™ services:
Preclinical evaluation of suppression of immunological and inflammatory responses
Through Panlabs, Eurofins has 25 years of experiences creating and working with a diverse set of in vivo efficacy models for inflammatory diseases. These models range from basic models of immune modulation, restoration, suppression and stimulation to specific models of inflammation-induced organ damage. All experimental models are tested in a dose-dependent manner with approved benchmark positive controls.
Our ability to deliver multi-faceted outcome studies, means that you will receive the data that is most appropriate for your program. We routinely measure relevant biomarkers (e.g., cytokines) employing our highly sensitive ImmunoSignal™ services; physiologic outcomes, like airway hyper responsiveness, and swelling; as well as more complex behavioral outcome measures such as scratching or mechanical allodynia or histopathology.
Rely on Eurofins to deliver the most meaningful preclinical data, allowing you to decide whether your candidates' efficacy meets the criteria for full clinical development.
Advantages of preclinical inflammation / allergy studies with Eurofins:
30 therapeutically relevant models, including:
Respiratory diseases affect the upper respiratory tract and can result in difficulty breathing, decreased lung capacity, asthma, emphysema and a host of other conditions. Left untreated, respiratory diseases can result in chronic breathing issues and become potentially life threatening.
Eurofins recognizes the need for effective and relevant in vivo models for respiratory conditions. In order to help you bring the next potential respiratory treatment to clinical trials, we offer a number of relevant qualified models to help you understand you candidate's effectiveness.
With more than 25 years of experience, our experts can provide you the data to give you confidence to take the next step in your project.
Advantages of preclinical respiratory studies with Eurofins:
In vitro services to find the next generation drugs to combat infectious disease
With the rising prevalence of drug-resistant microorganisms, effective and potent anti-infective agents are becoming increasingly more relevant in order to treat infectious diseases. Eurofins, through the expertise of Panlabs, identified this need over 25 years ago and has since been working diligently with the pharmaceutical industry to provide a robust portfolio of in vitro and in vivo anti-infective models to support the discovery and development of novel antimicrobial therapies.
Our in vitro portfolio follows the standard industry methods (CLSI) in order to evaluate the antimicrobial activity of your test agents. Our services have unmatched flexibility, allowing for combination testing, determining synergistic, indifferent, or antagonistic effects as well as resistance analysis to determine the rate at which organisms develop a non-susceptible phenotype which can have major clinical implications.
Using a comprehensive collection of over 270 clinically relevant Gram-positive and -negative bacteria (including multi-drug resistant, MDR, organisms), anaerobic bacteria, yeast, and filamentous fungi, Eurofins provides the support and experience that your anti-infective drug program needs to succeed.
Features of in vitro anti-infective services from Eurofins:
270 pathogens, including:
Cancer is a multi-dimensional disease driven by genetic instability and selective pressure to continue to persist. As such, an ever changing tumor presents a formidable challenge to effectively treat. Given this challenge, a strategy that continues to be employed is a multi-prong attack on the tumor to eliminate multiple traits and/or to prevent the tumor from developing resistance mechanism to circumventing treatment.
To support this multi-prong approach to cancer therapy, combinations of therapeutics (small-molecules or biologics) are tested on OncoPanel™ cell lines in a dose response matrix. This data format is ideal for a variety of downstream drug-drug combination analyses including calculation of combination index, isobolographic analysis, and determination of excess over Bliss independence.
Goals of for drug combination studies:
OncoPanel™ services provide multi-parametric drug response data across a panel of 300 genomically diverse cancer cell lines that span 19 different cancer tissues. Therapeutics may be tested in the entire panel or a subset that contains any combination of the 300 available cancer cell lines. Using high content imaging, simultaneous detection of anti-cancer activity and detection of pharmacodynamic biomarkers in a single, multiplexed assay may be provided.
OncoPanel™ services allow a detailed understanding of drug response that cannot be achieved by single endpoint assay profiling. Assay endpoints can be customized to measure up to four biological pathways or processes at once (cell viability, apoptosis, mitotic block and custom markers). Genomic analysis of OncoPanel™ data enables the discovery of predictive biomarkers to help determine which genomic features may predispose patients to therapeutic response.
Cell surface expression of your target antigen can be measured in live cells to correlate antigen expression with therapeutic response in the same assay. OncoPanel™ can also provide quantitative binding analysis of therapeutic antibodies within the same multiplexed assay.
Study design to match your project goals
As assays become more sophisticated, it is often necessary to tailor parameters to the specific question that is being asked. Our experience working with a variety of different molecules, such as kinase inhibitors, epigenetic modulators and large molecule biologics, ensures that we can generate the best study design for your project.
The OncoPanel™ Advantage:
300 genomically characterized cancer lines provides statistical power to uncover and rate predictive biomarkers
OncoPanel™ 3D – determine activity of compounds on tumor spheroids
OncoPanel™ 3D is a drug profiling platform comprised of ~100 cancer cell line models grown as three-dimensional (3D) tumor spheroids that phenocopy key attributes of human tumors. Drug testing is initiated only after spheroid formation has been confirmed through hypoxia-positive spheroid calling using high-content imaging. This platform provides a means to compare the tumor penetrating properties of a collection of drugs by comparing activity in 2D versus 3D cell culture.
Large molecule biologics
The types of therapeutics used to treat cancer are the most diverse among therapeutic areas. Of growing success and interest has been large molecule therapeutics for oncology, especially humanized monoclonal antibodies (mAbs). MAbs are generally targeted to cell surface receptors, or the ligands of these receptors, to block various oncogenic hallmarks (e.g., uncontrolled cell proliferation). OncoPanel™ services can help profile cell surface antigen expression for a mAb's target and identify drug responsiveness in the same assay
Epigenetic therapeutics
Druggable epigenetic modulators undergo oncogenic mutation and are seen as attractive therapeutic targets. However, inhibition of some epigenetic targets results in a significantly delayed drug response that is not revealed by conventional, short term cell growth assays. To address this issue, we have established two- and three-dimensional assay conditions with extended assay duration to yield robust cell line profiling data. While this assay design was specifically developed with epigenetic targets in mind, other slow-acting therapeutics are likely to reveal themselves employing this extended protocol.
Bioavailability of a compound is mainly determined by absorption, distribution, metabolism and excretion (ADME), which can be evaluated by a series of in vitro assays. In small molecule drug discovery the typical goal is to identify a low molecular weight compound which can be effectively administered via an oral route. The fraction of a dose after drug administration that reaches the general circulation intact is defined as its bioavailability.
There is a significant advantage to obtaining in vitro ADME data as early as possible in the drug discovery process. For example, hepatic metabolism is a primary determinant of pharmacokinetic behavior and rapid first-pass metabolism is a major cause of low bioavailability. In vitro ADME results serve as good indicators as to whether a compound will be bioavailable and assists in eliminating failures early in the development process. It also serves as a useful guide for later stage studies.
Eurofins offers a diverse set of in vitro ADME assays which, if applied early in the drug discovery process, can be used to prioritize compounds based on these properties and to select those compounds likely to have high bioavailability for further development.
Assessment assays for bioavailability:
Undesirable ADME properties are major factors causing failures during drug development. To prevent these costly failures from occurring, in vitro screening of potential drug candidates in the early drug discovery phase has been employed as a cost-effective approach to identify compounds with unfavorable ADME characteristics. Eurofins provides a wide variety of metabolism screening assays using assay matrices, including: recombinant cytochrome P450 enzymes (CYPs), recombinant uridine diphosphate-glucuronosyl transferases (UGTs), liver microsomes and hepatocytes from human and animal species.
After entering the body, a drug will be metabolized to one or several more water-soluble metabolites, which can be more readily excreted than the corresponding parent drug. The enzymes that catalyze chemical conversion during the metabolism process are categorized as phase I (mainly CYPs) and phase II (such as glutathione-S-transferases and UGTs) drug-metabolizing enzymes. These enzymes are present at high levels in organs of elimination, such as the liver, intestine, and kidney. Intrinsic clearance assays using liver microsomes or hepatocytes will allow you to estimate the extent of metabolic clearance and first-pass effect for your compounds. Further studies of CYP- and UGT-reaction phenotyping will allow you to understand whether your compound is subject to drug-drug interactions or polymorphic effect.
By partnering with Eurofins, you'll be able to better understand your drug candidate's metabolism and stability and obtain a more comprehensive assessment of that compound's drug profile.
In vitro metabolism screening assays allow identification of compounds that have these favorable characteristics:
Metabolism-mediated drug-drug interactions (DDI) refer to simultaneously administered drugs that interfere with each other's absorption, distribution, metabolism, and elimination (ADME) by changing activities of drug metabolizing enzymes and/or drug transporters.
As an example, drug A may inhibit or induce activity of an enzyme(s) or transporter(s) directly or virtual of it being a substrate of these proteins. As a consequence, another medicine, drug B, that is a substrate of those affected enzymes and transporters will have its PK profiles altered and vise versa.
DDI alters drug's pharmacokinetic (PK) profile and this change in concentration and duration profile may lead to either clinical ineffectiveness or adverse drug reaction in patients that can be severe or fatal. Both the FDA and EMA have issued guidances which recommends that all new drugs be investigated to understand their potential to interact with other drugs.
To address this need, Eurofins provides a wide range of assays to help our clients screen their compounds for drug-drug interactions. Early screening of DDI characteristics of a compound is critical in reducing late-stage failures.
Available DDI Profiling Assays:
Reversible protein phosphorylation is critical for normal cellular function with perturbations leading to diseases such as cancer. This post-translational modification alters protein function either by relocating proteins, changing protein interaction and/or modifying their enzymatic activity. Phosphatases are the key enzymes involved in removing phosphatase groups and thus reversing the effect of kinase directed phosphorylation. Although lagging behind kinases in maturity as a therapeutic drug class, interest is growing in phosphatases, like PTP-1B, as future therapeutic targets. As with kinases, phosphatase inhibitor specificity is a major challenge for drug discovery scientists.
Through the combined expertise of Cerep, Panlabs, and PhosphataseProfiler™ services, Eurofins has developed a robust, reliable, and well-characterized solution to screen your focused chemical libraries or profile your lead compounds for their inhibitory effects on phosphatases.
Advantages of Phosphatase Profiling with Eurofins:
Proteases are a class of enzymes which perform proteolysis, the mechanism of digesting or cleaving long chain proteins into smaller fragments by severing the peptide bonds that hold them together. Trypsin, a serine protease secreted by the pancreas, is commonly used in cell tissue culture to cleave the bonds that cells use to adhere to a flask.
Proteases also play a major role in disease. HIV-1 protease is essential to the viral replication process. MMP-9, a matrix metallopeptidase, plays a role in angiogenesis and is a therapeutic target for cancer. Because of their significance in the pathology of disease, proteases are a relevant drug target class.
Our broad portfolio of over 50 proteases spanning across the serine, cysteine, aspartic, and metalloprotease families was designed with you in mind to facilitate your drug discovery process and provide you with the answers you need.
Over 50 targets to support your research, including these families and targets:
Cyclic nucleotide phosphodiesterases (PDEs) are ubiquitously distributed throughout mammalian tissues and play a major role in cell signaling by hydrolyzing cAMP and/or cGMP. Due to their diversity and specific distribution at the cellular and subcellular levels, PDEs are able to selectively regulate various cellular functions. This regulatory ability implicates PDEs in various therapeutic areas including CNS, inflammation, and oncology.
As PDEs are expressed in a variety of tissues, selectivity is a prerequisite for a therapeutically viable PDE inhibitor. For example, high selectivity for PDE5 inhibitors is important for treating erectile dysfunction while minimizing possible side effects associated with inhibition of other PDEs. These possible side effects include tachycardia and vasodilation that are attributed to inhibition of PDE1 and PDE3, or blue-green vision disturbances that are attributed to inhibition of PDE6.
In order to meet the growing need for robust PDE profiling, Eurofins, through the expertise of Cerep and Panlabs, has designed an HTS platform to determine the inhibitory effects and selectivity of compounds on the PDE superfamily.
Advantages of PDE Profiling with Eurofins:
Nuclear hormone receptors (NHRs) are a large superfamily of ligand-activated transcription factors that consist of two subtypes, steroid and non-steroid. These receptors serve as on-off switches for genes which regulate cell differentiation, proliferation, and metabolism, and thus can play a role in the pathology of cancer, cardiovascular disease, inflammation, and reproduction. As with many receptors, ligand binding induces a conformational change in the receptor, but unique to nuclear receptors is their ability to up- or down-regulate gene expression. This ability makes nuclear receptors interesting therapeutic and liability targets.
Eurofins offers a broad portfolio of both binding and functional assays, including co-activator recruitment for nuclear receptors. These assays can help provide a complete profile of your drug or compound and give you a better sense of its gene-regulating features.
Advantages of nuclear receptor profiling:
Profile with the Industry's Largest Epigenetics Portfolio
Epigenetics, an increasingly popular field of drug discovery, is the study of heritable changes in gene expression that occur without changes in the DNA sequence. The epigenome is considered to be in constant flux and is responsive to environmental and pharmaceutically active molecules. Epigenetics-related enzymes and proteins catalyze the addition or removal of an array of covalent modifications on histone and non-histone proteins. For these reasons, epigenetics is becoming an increasingly important realm for drug therapies. Indeed, several drugs directed towards epigenetic modifying enzymes are already on the market with more in the clinic to treat cancer.
In 2012, ahead of all other CROs, Eurofins recognized the industry's upcoming need for a comprehensive epigenetics program containing all major families. To meet this growing need, we began to develop a range of target based assays using biologically relevant substrates (nucleosomes, histones, and peptides) to create the most meaningful assays. The majority of our proteins/substrates are produced in-house to ensure the highest quality of proteins resulting in high batch to batch reproducibility.
Eurofins' epigenetic toolbox is based on several technology platforms and allows for your choice of technology and/or substrates, providing added flexibility to meet all of your drug discovery needs.
Advantages of Eurofins' Epigenetics Program:
50 Writers, including: SMMT, Kinases, DNMT, HMT and HAT
40 Erasers, including: Demethylases, HDAC / sirtuin and DUB
45 Readers, including: Bromodomain and Methyl readers
17 Off-target and cell-based assays, including acetylation and methylation studies
Eurofins high quality and well characterized PrecisION® ion channel stable cell lines are the foundation of IonChannelProfiler™ services. From single-cell manual patch clamp, the gold standard in ion channel work, to high throughput 384-well automated electrophysiology instruments, we use our cells on a variety of platforms to provide the throughput or depth of analysis that matches your needs.
Advantages of Ion Channel Profiling with Eurofins:
Multi-prong Assessment of Cardiac Liability
Cardiotoxicity is a major cause of drug development failure and withdrawals. hERG screening alone cannot reliably detect potential cardiac adverse side effects. The Cardiac Safety Research Consortium (CSRC) recently proposed the Comprehensive in vitro Proarrhythmia Assay (CiPA), which would incorporate in vitro cardiomyocyte studies as a component of cardiac safety assessment. In addition to our CardiacProfiler™ services, our services using human cardiomyocytes fit into this emerging paradigm.
We have employed a combination of assay platforms along with Cytiva™ Plus human stem cell derived cardiomyocytes from GE Healthcare to address this need for more biologically relevant and predictive cardiac liability models. Eurofins offers complimentary approaches, including High Content Analsysis (HCA), Multiple Electrode Array (MEA) and manual patch clamp assays, to reliably detect and characterize cardiac safety risks.
Using a population of beating cardiomyocytes, MEA provides ECG-like field potentials to detect proarrhythmic events, alterations in beat rate and other adverse effects. Changes in field potential duration is related to alterations of the QT interval, which in a clinical setting may initiate a potentially fatal Torsades de Pointes (TdP) arrhythmia.
Manual patch clamp studies provide a detailed assessment of action potential duration on individual cardiomyocytes. Specifically, ventricular-type cells within the general cardiomyocyte population can be tested. This is important as the ventricular-type cardiomyocytes are relevant for ventricular dysfunction, a major form of cardiotoxicity.
Imaging techniques using cardiomyocytes measure cell health parameters resulting from structural damage upon prolonged compound treatment, toxic effects that may not be otherwise identified by electrophysiological methods. Multiple parameters, including cell number, intracellular calcium flux, mitochondrial membrane potential and membrane permeability can be measured on live cells to determine changes in normal cellular functions. Alternatively, fixed cells are used to reveal appearance of peri-nuclear BNP expression, α-actinin disruption, troponin I integrity and reduction in cell number to further demonstrate toxic effects.
Advantages of Cardiotoxicity Assessment with Eurofins:
Beyond hERG for cardiac liability testing
Gain a broader insight into potential cardiac risk with earlier profiling of new chemical entities at throughputs that are more appropriate for lead discovery and optimization. CardiacProfiler™ is a comprehensive cardiac safety panel that includes each of the key cardiac channels, providing a robust, cost-effective approach to cardiac liability testing.
Many withdrawn drugs have been shown to block the human ether-a-go-go (hERG) channel, delaying repolarization of the cardiac action potential and leading to prolongation of the QT interval on an electrocardiogram. This can potentially initiate the arrhythmia known as Torsades de Pointes (TdP) with fatal consequences. While hERG is an important factor for cardiac liability, it is not the only factor. Excitation and relaxation of cardiac muscle is regulated by a variety of different ion channels. Some of these channels are genetically linked with long QT syndrome, suggesting that their modulation by drugs could also produce life-threatening arrhythmias independently of hERG. Conversely, a number of relatively potent hERG channel blockers do not induce TdP. Many of these drugs (e.g. verapamil, amiodarone) have mixed channel blocking action which may ameliorate the effects of hERG blockade. Thus, hERG screening alone may be insufficient to flag potential cardiac liability. Conversely, abandoning promising compounds based on hERG blockade alone may result in failing potentially safe clinical drugs.
In support of this philosophy, a recently output of the Cardiac Safety Research Consortium (CSRC) was a proposed shift in cardiac safety assessment to include a Comprehensive in vitro Proarrhythmia Assay (CiPA). CardiacProfiler™ services as well as our related cardiotoxicity assays using human cardiomyocytes fit into this emerging paradigm.
Advantages of Cardiac Risk Profiling with Eurofins:
In additional to playing play a major role in the metabolic fate of drugs, cytochrome P450 (CYP) enzymes are major targets in drug-drug interactions (DDIs). Drug induced inhibition of CYP enzymatic activity is one important cause for DDI, but it not alone sufficient to assess the potential to induce DDI. CYP enzymes can be transcriptionally induced by many xenobiotics including some drugs, through the mediation of nuclear receptors. Therefore, understanding the potential of new molecular entities (NMEs) to induce CYP expression is important to minimize DDI liability.
CYP induction is traditionally determined by measuring enzymatic activity in cultured primary hepatocytes; however, due to enzyme inhibition, cytotoxicity, or other effects, this assay is prone to false negatives. In order to address the growing need for robust, sensitive assays to measure CYP induction, Eurofins has developed CYP assays which measure the mRNA level of the targeted CYP genes. As the preferred method to measure CYP induction, mRNA analysis is less prone to false negatives than traditional activity-based assays and follows FDA and EMA Guidance (2012).
Advantages of CYP induction profiling with Eurofins:
Transporter studies for ADME and therapeutic activity
Transporters are membrane proteins that control the influx and efflux of essential nutrients, ions, neurotransmitters, cellular waste, environmental toxins, and other xenobiotics such as drugs. Drug transporters are composed of two major super families: ABC (ATP binding cassette) and SLC (solute carrier) transporters.
ABC transporters mediate unidirectional efflux and are primarily active transporters as they directly rely on ATP hydrolysis to pump their substrates across membranes. They play major roles in hepatobiliary and urinary excretion of drugs from the blood to the lumen, intestinal absorption of drugs, and in brain blood barrier penetration of drugs.
SLC transporters mediate either drug uptake or efflux and can be facilitated transporters or secondary active transporters, which transport drugs using energy produced by transmembrane movement of other solutes in accordance with their concentration gradient. They play major roles in hepatic and renal uptake, and urinary excretion. Some SLC transporters, such as those for neurotransmitters, are also important drug targets themselves with clinical drugs treating various psychiatric disorders.
Transporters play a significant role in a drug's clinical efficacy and safety. Eurofins, through the expertise of Cerep and Panlabs, has developed robust transporter uptake and inhibition assays to allow quick and cost-effective screening of new molecular entities (NMEs) for their interactions with these transporters.
Advantages of transporter screening with Eurofins:
Transporters for drug absorption and disposition
Drug transporters are essential in controlling the absorption and disposition of xenobiotics, including pharmaceuticals. As such, transporters play a key role in defining the clinical efficacy and safety of drugs.
ABC (ATP binding cassette) transporters, including members like P-gp and BCRP transporters, play major roles in hepatobiliary and urinary excretion of drugs from the blood to the lumen, intestinal absorption of drugs, and in brain blood barrier penetration of drugs. SLC (solute carrier) transporters, including members like OATP1B1 and OAT1, play major roles in hepatic and renal uptake, and urinary excretion.
Interaction with these efflux or uptake transporters can play a significant role in a drug's pharmacokinetic properties and, in turn, its efficacy and safety profile. Eurofins, through the expertise of Cerep and Panlabs, has developed robust in vitro transporter inhibition assays to assess potential drug-drug interactions prior to costly clinical assessment.
Advantages of Drug Transporter Screening:
Screening for therapeutic activity or selectivity profiling off-target liability
Neurotransmitter transporters, especially biogenic amine transporters, have been a highly successful target class for clinical therapeutics. First generation Selective Serotonin Re-Uptake inhibitors (SSRIs) are one of the most recognized class of drugs to treat depression. While next generation anti-depressants with polypharmacology (activity across multiple targets) for serotonin and norepinephrine may offer better clinical activity.
Like most drug targets, unwanted interaction with neurotransmitter transporters may lead to adverse reactions. Therefore, profiling compound activity against neurotransmitter transporters is also important for general liability assessment.
Eurofins, through the expertise of Cerep and Panlabs, have both binding and cellular uptake assays to test compounds for interaction against this class of clinically important targets.
Advantages of neurotransmitter transporter screening with Eurofins:
Ion channels are well known for regulating electrical activity in excitable cells, and many roles in non-excitable tissues continue to be uncovered. They are important therapeutic targets in a range of indications including arrhythmia, hypertension, local anesthesia, pain, stroke, epilepsy, depression, bipolar disorder, COPD, autoimmune disorders and diabetes. Not only are ion channels important drug targets, but they are also generally relevant for drug safety. Indeed, many drugs withdrawn from the market due to cardiac related adverse effects have been shown to block the human ether-a-go-go (hERG) ion channel, which delays repolarization of the cardiac action potential and can result in a potentially fatal arrhythmia known as Torsades de Pointes (TdP).
Through the combined expertise of Cerep, Panlabs, and IonChannelProfiler™ services, Eurofins offers a broad portfolio of both binding and functional assays for ion channels. Our years of experience as an ion channel CRO has enabled us to better understand our customers' latent needs, so if you're looking for an ion channel screening solution, you've found it.
Advantages of Ion Channel Profiling with Eurofins:
Ubiquitination is a key regulatory mechanism which attaches the small protein modifier ubiquitin to protein substrates, thereby modifying their structure, function, cellular location, or targeting them for destruction via proteolysis. Inappropriate regulation of ubiquitination pathways is linked with a number of human diseases. In recent years, components of these pathways have emerged as a new and relatively untapped class of targets for drug discovery, with applications in cancer, neurodegenerative disorders such as Alzheimer's and Parkinson's disease, viral infection, diabetes, and inflammation.
Eurofins has removed the complexity of drug discovery in this emerging area by providing assays for both ubiquitination and de-ubiquitination, with off-the-shelf assays for functional E3 ligase cascades, we have made this target class readily accessible for research and drug discovery.
Advantages of Ubiquitin Profiling with Eurofins:
Profile functional E3 ligase cascades
While ubiquitination offers an exciting new avenue to approach many difficult-to-treat diseases, there are certain aspects of ubiquitination that have provided an obstacle to drug development. The first complexity is that, unlike other post-translational modifications (e.g., phosphorylation), ubiquitination relies on several interconnected steps involving multiple enzymes (i.e., E1, E2 and E3). Secondly, while E3 ligases are the most attractive targets because of their potential specificity, they are the most complex - sometimes consisting of multiple protein constituents. Furthermore, many of the substrates themselves need to be post-translationally modified before they are recognized as substrates for ubiquitination.
Eurofins overcomes the restrictions to ubiquitination drug discovery. By applying our protein production and assay expertise, we've developed a suite of assays to measure distinct ubiquitination cascades. Each assay contains the complete complement of ubiquitin enzymes (E1 activating enzyme, E2 conjugating enzyme and E3 ligase) and a biologically-relevant substrate with appropriate post-translational modifications. The incorporation of ubiquitin into the substrate is quantitatively detected by electrochemiluminescence, which allows for the identification of inhibitors and activators.
Advantages of UbiquitinProfiler™:
Deubiquitination (DUB profiling)
Analogous to phosphatases' role in reversing phosphorylation of proteins, the deconjugating enzyme (DCE) proteases, including deubiquitinating enzymes (DUBs), similarly reverse the ubiquitin modification of proteins. By removing ubiquitin from target proteins, DUBs act to oppose the effects of ubiquitination on protein function or targeted destruction by the proteasome.
Advantages of DUB profiling with Eurofins:
Early & Late Panel Assays
Providing critical early assessment across a range of targets, our safety and liability service panels use a combination of functional and binding assays to empower you to make better decisions. When you know everything you can about your drug candidates, including potential off-target liabilities, you'll avoid costly setbacks and develop more promising compounds, faster.
Each of our safety and liabilities panels were specifically chosen for their relevance to critical diseases and biological processes, including neurotoxicity, cytotoxicity, cardiac function, immunoprotection, diabetes, inflammation, and gastrointestinal functions. These panels can provide early identification of potential adverse activity in order to help you optimize your drug's safety margins.
Profiles matched to the stage of your project:
G protein coupled receptors (GPCRs), also known as seven transmembrane receptors (7TMs), have been and will continue to be prominent drug targets for treating hypertension, pain, asthma, neurological and other disorders. Indeed, as 40% of pharmaceuticals target a small fraction of the family, GPCR profiling continues to maintain an important role in the realm of drug discovery and development.
Eurofins has all the solutions for your receptor screening and GPCR profiling needs through the combined expertise of Cerep, Panlabs and GPCRProfiler® services . Whether you're looking for binding assays, functional profiling or secondary messengers, we have you covered. If you're embarking on a new project and want to outsource an HTS campaign, SAR or general selectivity profiling of your leads and candidates, we have a receptor profiling solution for you.
Advantages of GPCR profiling with Eurofins:
Radioligand Binding Services
Radioligand binding is the gold standard method for detecting compound interaction with GPCRs, allowing for the simplest interpretation of assay results. A favorite of medicinal chemists, radioligand displacement assays can be used for simple yes/no interaction determination or to calculate a compound's affinity for a receptor of interest. Along with functional assays, binding studies can provide a complete profile of a compound's in vitro pharmacology.
Eurofins is the market leader for outsourced radioligand binding studies. With origins in Cerep and Panlabs, we have been successfully conducting GPCR binding studies for decades. Our binding assays use the gold standard filtration method for highest assay robustness. The majority of our assays are conducted with membrane preparations produced in-house to control for the quality of these critical reagents and ensure data reproducibility.
Cell-based assays for GPCRs
When assessing a GPCR therapeutic's potential efficacy and liabilities, it is important to understand its on and off target activity. GPCRs can signal through a variety of cascades and a drug will activate, inhibit, or modulate one or more of these. Indeed, compound activity can be complex as certain compounds may elicit different activity on different signaling cascades, also known as ligand biased signaling. Eurofins has services covering several second messenger pathways to better understand compound activity. Along with binding assays, these functional assays can provide a complete profile of a compound's in vitro pharmacology.
GPCRProfiler® services is the first complete cell-based functional GPCR profiling platform that uses a common validated readout for over 165 GPCRs. The foundation of GPCRProfiler® is our ChemiScreen™ GPCR stable cell lines that are used for real-time calcium flux assays to rapidly, reliably, and reproducibly screen and profile compounds. Using one platform allows ligands to be screened for agonist and antagonist activity using identical buffer conditions and incubation times for the entire spectrum of GPCRs for easy high throughput analysis and comparison.
Our cell based assays feature multiple second messenger readouts, including cAMP for Gi and Gs coupled receptors as well as IP1 and IP3/calcium flux for Gq coupled receptors, emphasizing the natural pathway of the receptor. Additionally, we also have label free cell based assays to look at endogenous receptor signaling as well as traditional GTPγS assays.
Together, our collection of functional assays, along with our binding studies, can provide an orthogonal approach to confirm the in vitro pharmacology of your compounds.
GPCR Profiling for Allosteric Modulators
Historically, GPCR drug development has been focused on compounds that interact with the receptors' orthosteric site; however, the orthosteric binding site can be highly conserved, making it extremely difficult to generate receptor-specific compounds.
Researchers circumnavigate this restraint by exploiting the receptor's allosteric sites. Allosteric compounds are gaining relevance because they can modulate receptor activity, allowing greater physiological control of receptor activation, and are predicted to be more selective and have a reduced potential for overdose.
Our AllostericProfiler™ receptor profiling services use a functional readout to detect allosteric compound activity. AllostericProfiler™ is the first fully validated selectivity profiling service capable of detecting a range of compound activities for over 165 GPCRs by using a unique two-addition methodology to detect of a wide variety of activities including agonist, positive allosteric modulator (PAM) and negative allosteric modulator (NAM) activity.
AllostericScreener™ screens compound libraries to identify new compounds having positive allosteric modulator (PAM) activity for a target of interest. AllostericScreener™ service employs an assay design that is similar, but slightly modified, to our standard GPCRProfiler® services. This assay design can identify both agonist and PAM activities. Therefore, you can discriminate hits that either activate the receptor directly, modulate the receptor's activity or those that have a mixture of these activities.
Drug discovery efforts are usually centered on a single target against which compounds are optimized for therapeutic efficacy. However, developing a selective kinase inhibitor is particularly challenging, because of conserved active sites and high structural homology between kinases. Broad profiling, for many, has become a requirement of new kinase inhibitor programs for better understanding structure/activity relationships, helping to avoid targets with toxic liabilities, and, ultimately, to select better drug candidates. The last five years have seen eight anti-cancer kinase inhibitors receiving FDA approval, increasing recognition of kinases as a vital drug target class.
Through the combined expertise of Cerep, Panlabs, KinaseProfiler™, and SignalProfiler™ services, Eurofins offers an unmatched portfolio of biochemical and cellular kinase assays.
Advantages of KinaseProfiler™ services:
Benefits of profiling cellular kinase activity with Eurofins:
70 Singleplex and >20 Multiplex assays
Eurofins has the experience and skills needed to bring you early stage pharmacokinetic (PK), oral bioavailability and blood-brain barrier (BBB) data to evaluate your new molecular entity. PK and BBB studies are prerequisite for interpreting preclinical efficacy and toxicology results. Using qualitative measurements of drug exposure, we can provide a solid interpretation of preclinical efficacy. PK data can also help in species selection and design of preclinical toxicology studies.
Eurofins will work with you to understand the physicochemical properties of your test material to develop a dosing and sample collection strategy that will provide you with the most meaningful data. We can obtain blood and/or tissue (e.g. brain) samples following dose administration (IV, PO, IP, IM, SC, IN, and ICV, also short- or long-term continuous infusions) and both serial sampling for PK and parallel sampling for PK, BBB or combined PK-BBB are available. PK/PD studies can be combined using our broad portfolio of pharmacodynamics models.
PK/BBB dosing and sampling studies can be paired with standard or custom bioanalytical methods to provide a concentration versus time curves to provide a complete pharmacokinetic profile for your compound.
Advantages of in vivo pharmacokinetic and blood/brain barrier studies with Eurofins:
Cardiovascular disease (CVD) is one of the leading causes of death for both men and women worldwide. CVDs affect the heart and blood vessels, leading to a variety of conditions including ischemia, stroke, heart attack, angina and cardiomyopathy. Eurofins, through the expertise of Panlabs, has been conducting in vivo testing for cardiovascular disease using in vivo models for both side-effect profiling and efficacy for over 25 years.
Our staff, with their vast experience, is dedicated in assisting you to properly evaluate your lead series and clinical candidates. We offer a number of relevant cardiovascular disease models, including models of hypertension, thrombosis and arrhythmia.. We can also provide many related ancillary services such as measuring relevant cytokine biomarkers in plasma though our highly sensitive ImmunoSignal™ services, measure lipids or perform blood chemistries.
Whether you are trying to evaluate potential cardiovascular liabilities during lead optimization or trying to verify in vivo efficacy, Eurofins can provide you high quality and reproducible results to progress your drug discovery program.
Advantages of Eurofins' cardiovascular in vivo studies:
In addition to our expansive portfolio of functional ion channel assays, we offer radioligand binding assays across a number of ion channel families including sodium, potassium, and calcium. Radioligand displacement assays can be used for a yes/no interaction determination or to calculate a compound's affinity for a channel of interest. Along with functional assays, binding studies can provide an orthogonal approach to creating a complete profile of your compound's in vitro pharmacology.
Our binding assays use the gold standard filtration method to produce highest assay robustness. Our ion channel binding assays are conducted with membrane preparations produced in-house to control for the quality of these critical reagents and to ensure tight data reproducibility. Radioligand binding assays are a useful approach for monitoring potential hERG liability at the earliest phase of drug discovery. Here, the primary aims are to raise flags which could trigger follow-up studies, such as electrophysiological screening.
Advantages of Ion Channel Binding with Eurofins:
Eurofins Villapharma provides the biopharmaceutical industry with high quality organic synthesis expertise and unique collections of novel, patentable, drug-like organic compounds for drug discovery. Our teams, of more than 80 chemists, are experts in high-quality Organic Synthesis, Medicinal Chemistry Services, Screening Libraries, and the production of unique collections of novel organic molecules with potential biological activity. Our proven experience in developing Screening Libraries has resulted in new chemical starting points for multiple client discovery programs, including those in the Anti-infective, Oncology, CNS and Metabolic Disease therapeutic areas.
With our state of the art facilities, a production technology that is based on rapid parallel synthesis by using specially designed versatile workstations, and a large and interesting portfolio of privileged core structures, our platform allows us the ability to cover a wide range of different chemistries. The Eurofins Villapharma chemists leverage their high level of problem solving skills to manage programs needing complex chemistry and our chemists are recognized for the strong expertise they have developed in heterocycles, macrocycles, peptides/peptidomimetics, and natural product-like chemistry.
Our team follows established processes and Standard Operating Procedures (SOP’s), and has the necessary tools required for optimal data and project management. Furthermore, the team has a proven track record of handling confidential data and exchanging of files through secure file sharing systems. Data and records are supported through a proprietary Electronic Lab Notebook system in order to ensure reproducibility, quality control, and management of intellectual property.
DiscoverX Drug Discovery Services
Our portfolio of drug discovery services and screening solutions are designed to support you at every stage of development - from HTS & library profiling, to lead optimization and preclinical development. Powered by our EFC and competition binding technology platforms, we offer the largest portfolio of biochemical and functional cell-based assays. Reduce the time and cost of your discovery programs by taking advantage of our expertise and innovative technology platforms to find a solution that meets your project needs.
LeadHunter® Drug Discovery Services Portfolio:
SAFETYscan™ In Vitro Pharmacological Profiling Services
In vitro pharmacological profiling is increasingly being used earlier in the drug discovery process to identify undesirable off-target activity profiles. SAFETYscan services offer a broad menu, including the assays recommended by major pharmaceutical companies (Bowes et.al. 2012). All SAFETYscan assays are human orthologs and provide functional data for efficient decision making, while other commercial panels are primarily binding assays for humans and rodents. Assessing the specificity of lead compounds early in development using highly relevant and predictive assays allows more informed decisions about compound safety, ultimately leading to the development of safer and more effective drugs.
SAFETYscan Services Offerings:
Safety44™ panel of functional assays with all human targets for safety screening are now available. Additionally, DiscoverX offers the broadest portfolio of GPCR and kinases targets to meet your safety screening needs.
SAFETYscan In Vitro Pharmacological Profiling Services Highlights:
-Better confidence using human target assays versus rodent orthologs
-Functional data to support SAR analysis in lead optimization
-Reduce expensive follow up studies
BROMOscan® Epigenetic Screening & Profiling Services
DiscoverX offers a suite of assays for epigenetic targets to enable identification and classification of inhibitors based on potency, selectivity and in vitro efficacy. BROMOscan, is an industry leading collection of 40 validated, quantitative binding assays for identifying small molecule bromodomain inhibitors. Bromodomains are epigenetic “reader” proteins that have emerged as an important new druggable target class in small molecule inhibitor drug discovery with several bromodomain-containing proteins being associated with disease.
bromoMAX℠ - Largest Bromodomain Assay Panel
With a panel of 32 bromodomain assays, bromoMAX includes the entire BET family along with other diverse bromodomains including ATAD2, BAZ2A, CREBBP, SMARCA2, PBRM1(5), TAF1L and others. This comprehensive collection of validated assays virtually eliminates assay development bottlenecks and provides a comprehensive selectivity screening tool that can accelerate the identification and optimization of potent and selective small molecule bromodomain inhibitors.
DiscoverX® Discovery Services provides you access to a comprehensive collection of cell-based pathway indicator assays designed to detect activation or inhibition of complex signal transduction pathways in response to compound treatment. Based on the proven PathHunter® technology, these stable cell lines allow you to measure distinct events within a variety of pathways involved in compound toxicity, cholesterol metabolism, antioxidant pathways, DNA damage, ER stress and many others to drive your lead discovery and optimization without relying on reporter gene assays or complex phenotypic screens.
Comprehensive Menu
PathHunter® Pathway Assays are novel, non-imaging functional whole cell assays for measuring multiple cellular signaling events such as protein translocation, secretion, degradation and expression using highly sensitive and quantitative chemiluminescent detection. This approach can be applied to any cell signaling cascade in which a target protein either degrades, translocates or is secreted. These assays serve as pathway indicators.
Panel Highlights and Benefits
BCL2scan: Biochemical ligand binding assays for anti-apoptotic BCL2 family members
Biochemical Ligand Binding Assays for BCL2, BCLXL, BCLW, BCL2A1 and MCL1
DiscoverX has developed a best in class comprehensive panel of quantitative biochemical ligand binding assays for anti-apoptotic BCL2 family proteins that can be used to identify and to optimize therapeutic small molecule inhibitors targeting proteins from this target class. The BCL2 family of proteins determine the commitment of cells to apoptosis and are emerging therapeutic targets for oncology, auto-immune disease, neurodegeneration, and aging-related morbidities. The BCL2 family consists of pro-apoptotic and anti-apoptotic members that interact to regulate the MOMP pathway to apoptosis. The anti-apoptotic family members are the focus of many drug discovery efforts and include BCL2, BCLXL, BCLW, BCL2A1 and MCL1.
The DiscoverX BCL2 family assays enable measurement of potency and selectivity across these anti-apoptotic family members. You can screen, profile and measure Kd values in one flexible format in both high or low-throughput modes.
Platform Benefit & Technology Details
How the Technology Works
Compounds interacting with the BCL2 family protein prevent binding of these proteins to an immobilized known peptide ligand and reduce the amount of target protein captured on the solid support (Panels A & B). Conversely, test molecules that do not bind the BCL2 family protein have no effect on the amount of target protein captured on the solid support (Panel C). Screening “hits” are identified by measuring the amount of BCL2 family protein captured in test versus control samples by using a quantitative, precise and ultra-sensitive qPCR method that detects the associated DNA label (Panel D). In a similar manner, dissociation constants (Kds) for test compound-BCL2 family protein interactions are calculated by measuring the amount of target protein captured on the solid support as a function of the test compound concentration. Assay conditions are optimized for the measurement of true thermodynamic test compound Kd values.
DiscoverX offers a convenient bulk cell scale up option with the purchase of any PathHunter® or cAMPHunter™ clone. Package sizes range from 100 million to 10 billion cells. Cells are functionally tested for optimal assay performance and are confirmed to be Mycoplasma-free. Combine frozen, assay-ready bulk cells with PathHunter® certified Reagents and Control Ligands to expedite your screening campaigns and ensure optimal and reproducible results every time.
Rapidly growing use of cells for high-throughput screening (HTS) has posed a number of challenges including batch performance variation, cell production scheduling, capability and capacity management.
DiscoverX offers the solution – a convenient scale up service for any PathHunter®, cAMP Hunter™ or InCELL Hunter™ cell line. We provide single batches of cells in custom package sizes ranging from 50 million to 10 billion cells, quantities sufficient for complete screening campaigns, effectively decoupling cell production from screening. These cells undergo the same rigorous testing as our portfolio products, i.e., they are functionally tested to ensure optimal performance and stability, and are guaranteed to be Mycoplasma free.
Ensure speed and success in your screening campaign through the use of our single batch cell production service.
Key Features and Advantages
The T Cell Autoimmune Panel includes BioMAP systems comprised of complex co-cultures of immune and adherent human primary cell types. These cell-based assay systems model adaptive immune cell microenvironment and T and B cell responses in a platform amenable to compound screening. BioMAP technology measures physiologically relevant biomarker readouts (proteins, small molecule mediators, etc.), which permits insight into biological mechanism of action, efficacy and safety related effects of compounds.
Service
Description
Deliverables
BioMAP® Diversity PLUS Panel
Diversity PLUS consists of 12 BioMAP Systems containing early passage primary human cell types from multiple tissues that represent a broad range of human biology relevant to multiple therapeutic areas. Cells are cultured alone or as co-cultures and stimulated with a combination of factors to recapitulate the multi-component signaling networks associated with disease states. Compounds are interrogated in these systems to determine their phenotypic impact on physiologically relevant disease biology in terms of efficacy and safety.
Drug Discovery Applications
Diversity PLUS Advantages
Service
Description
Annotation Identification and biological intrepretation of relevant BioMAP activities
Similarity Search Results from unsupervised search for a biologically similar compound from the BioMAP reference database of >3000 compounds, biologics, approved drugs and experimental agents
Benchmarking Direct comparison of test agent to a specified reference compound from the BioMAP Database
Deliverables
Interleukin Screening & Profiling- ILscan
Discover Molecules that Activate or Inhibit Interleukin Receptors
DiscoverX offers cell-based assay services for interleukins that are highly specific and can be used to identify molecules that activate or inhibit Interleukin receptors and enable rapid development of drugs targeting immune-system disorders. These assays can be used to determine potency or rank ordering of potential hit or lead molecules.
During compound profiling, BioMAP analysis can identify unexpected drug activities and potential toxicities at an early stage in discovery. This knowledge will inform and complement animal studies, but most importantly it will provide insight into the safety-related effects of compounds on human biology before more costly stages of development. Assays based on cell lines and simpler cell –based models can miss these findings. BioMAP Systems can detect and distinguish a range of biological mechanisms associated with cellular and specific human toxicities, including those that are difficult to detect or de-convolute by target-based assays such as cell dysfunction (stress response), immunosuppression: B cell, T cell, mitochondrial dysfunction, microtubule function and many more. We have been working since 2007 with the EPA as a contractor for the EPA's ToxCastTM program. EPA launched the ToxCast™ program to develop ways to predict potential toxicity of chemicals and to develop a cost-effective approach for prioritizing the thousands of chemicals that need toxicity testing.
BioMAP® Tox Alert™ Analysis
iONCscan Services for Checkpoint Receptors- iONCscan
Evaluate Potency, Stability, or Rank Order Drug Molecules
DiscoverX’s iONCscan services offer an expanding menu of cell-based assays that can enable screening & potency determination for new immunotherapy drugs. Assays include signaling assays for PD1, OX40, CD137 and an expanding menu of targets. Assays are specific and sensitive and most show biologically relevant responses and can be used for the discovery of small molecules or biologics.
Tubule Epithelial Cell Toxicity
BTSC83 Subcutaneous Xenograft Mouse
U87-TARTK Subcutaneous Xenograft Mouse
U373 Subcutaneous Xenograft Rat
DSS-induced colitis in mice
DNBS-induced colitis in rats
TNBS-induced colitis in mice and rats
Business Development, Marketing & Operations Services
Business Operations and Logistics Support Services
Pharmacology Services
Data Analysis Services
Data Services
Statistical Analysis Services
"Very easy to work with. High quality results delivered in a timely manner."
"Fast turn around time, always happy to work with Eurofins."
"There is one big reason - Brent Hehl. Have worked with him for last 7 years on Abbvie CF project - his level of support is something that is highly valued. The data quality from Eurofins is another reason to work with them again in future."
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"Yes. Eurofins has high quality assays and a great customer support team."
"They are a wonderful company to work with. Always respond on time and are very efficient with producing the data in a timely manner."
"They provided high quality work and excellent report. Thanks"
"Eurofins was quick to respond and get things setup. The reports are clear and thorough. I plan to work with them again in the future for our in vitro testing needs."
"Eurofins was quick to respond, clear in their requirements, and provided data on time exactly as requested. I certainly plan to work with Eurofins again."
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