Cyprotex, an Evotec company, has sites at Alderley Park near Macclesfield, UK and in Watertown near Boston, USA. The company has dedicated and highly qualified employees with proven experience in a wide range of specialist techniques acquired across diverse industries. The majority of our clients focus in pharmaceutical research, however, we also support clients in the chemical, cosmetics and personal care and agrichemical industries.
Cyprotex specialises in in vitro and in silico ADME-Tox services. This includes in vitro ADME screening to support discovery projects, regulatory in vitro ADME and DDI studies during preclinical and clinical development, specialist mechanistic in vitro human and animal toxicity models (e.g. 3D models and MEA electrophysiology) and PBPK/QSAR modelling expertise. As well as supporting clients directly, we have a strong focus on R&D and our scientists regularly present our findings at scientific conferences and through publications.
In August 2017, Evotec acquired Aptuit in order to further expand the Group’s capabilities. As well as additional complementary drug discovery capabilities, Aptuit offers full CMC and IND-enabling services allowing the Evotec Group to provide expert support across the value chain from early discovery through to preclinical development and beyond.
UGT Inhibition IC50 Determination
nderstand the potential drug-drug interaction (DDI) liability of your compound by using our human UGT inhibition assay.
Uridine glucuronyl transferases (UGT) are a family of Phase II enzymes which play a major role in drug metabolism.
Inhibition of UGT enzymes has the potential to produce increased levels of endogenous bilirubin in the circulation which can lead to adverse toxicological effects.
Human UGT inhibition is one of Cyprotex's in vitro experimental ADME services. We deliver consistent and high quality data with the flexibility to adapt protocols based on specific customer requirements.
Understand the drug metabolism of your compounds by using our microsomal stability assay to measure in vitro intrinsic clearance or to identify any metabolites formed.
Subcellular fractions e.g., liver microsomes are useful in vitro models of hepatic clearance as they contain many of the drug metabolising enzymes found in the liver. Microsomes have the advantage that they can be pooled from multiple donors, are easy to prepare and can be stored for long periods of time. Due to the fact they are easily adaptable to high throughput screens, large numbers of compounds can be screened rapidly and inexpensively.
Microsomal stability is included in our portfolio of in vitro ADME screening services. We deliver consistent, high quality microsomal stability data with cost efficiency that comes from a highly automated approach and a focus on state of the art technology.
Cyprotex use the Applied Biosystems 7900HT system to monitor and quantify either up-regulation or down-regulation of genes. These effects may be a consequence of disease, drug- or chemical-induced effects or physiological effects.
A shift between respiration and glycolysis is observed in several pathological states including cancer, obesity, diabetes, and mitochondrial, cardiovascular, and neurodegenerative diseases. Cellular bioenergetics also play a role in aging, immune response, hypoxia and drug toxicity. The Seahorse Flux Analyser measures the metabolic phenotype of cells by simultaneously quantifying respiration and glycolysis in real time. Cyprotex is able to develop methods using the Seahorse XFe Flux Analyser to investigate specific disease states and the mechanisms behind the cellular bioenergetics effects.
Microelectrode Array Neurotoxicity and Cardiotoxicity Assays
Microelectrode array instruments monitor whole cell electrophysiology allowing multiple ion channels to be monitored simultaneously. Cyprotex has developed cardiac and neuronal models using iPSC-derived cardiomyocytes and cortical neurons respectively.
High content screening uses fluorescent dyes, fluorescently labelled antibodies or reporter based fluorescent protein systems to track processes or components within the cell. Cyprotex can offer both conventional and confocal high content screening techniques, the latter being beneficial for imaging 3D cell models. We have previous experience developing many phenotypic screening assays as well as novel protein-protein interactions target screening assays:
Cyprotex regularly design and develops new assays for our clients. We typically employ a 4 stage process:
Step 1: Our experienced scientists evaluate your needs and discuss the scientific rationale of the project and how your goals can be achieved.
Step 2: We plan and design an assay to match your requirements. We jointly establish the development process and validation criteria.
Step 3: We screen your test articles in the assay using robust QC processes within short turnaround times. We can assist in training, transfer and cross validation of the assay to a client’s site with ongoing support if required.
Step 4: Our reporting options are flexible – ranging from full written reports to customised data formats which can feed directly into your databases. We can assist you in interpreting the data and highlighting potential next steps.
Drug toxicity, often manifested as liver toxicity and cardiotoxicity, is a key reason for drug attrition. Identifying potential toxicity at an early stage in drug discovery can save both time and developmental costs, and most importantly reduce the likelihood of late stage failure.
Cyprotex is the ideal partner to assist you in understanding the toxic liability of your compounds using a panel of different techniques. We can help identify which compounds have the optimal ADME and safety profile to advance into the clinic. Our focus on state of the art technology and automation allow for high quality data to be generated rapidly and cost-effectively.
To that end, Cyprotex have invested in several high content screening (HCS) platforms that use automated fluorescence imaging to simultaneously analyse multi-parametric indicators of cytotoxicity. This improves the prediction of toxicological events and allows for a better understanding of the mechanisms of drug toxicity.
Our CellCiphr® technology was acquired from Cellumen in 2010. The technology provides a thorough assessment of potential mechanisms of toxicity using a HCS platform and links to exposure (Cmax) levels to understand the clinical relevance of the data. In 2013, we launched a new assay (eCiphr®Cardio) to evaluate cardiotoxicity in human iPS cell-derived cells using microelectrode array. This service has the advantage that it determines whole cell electrophysiology for all major ion channels in synchronously beating cardiomyocytes. Using the same microelectrode assay platform, we have also developed a new assay (eCiphr®Neuro) to evaluate neuronal activity using primary cortical neurons.
Cyprotex offer a number of other services including reactive metabolite detection using trapping agents, drug-induced phospholipidosis and steatosis, lysosomal trapping, hemolysis, mitochondrial toxicity using the Glu/Gal assay or using the Seahorse analyser, respiratory irritation, hERG inhibition using automated patch clamp, single end point cell viability endpoints (e.g., MTT, neutral red and LDH), toxicological gene regulation using qRT-PCR and a range of drug-drug interaction screens (available via Cyprotex ADME services). Cyprotex can also assess the potential genotoxicity of your compound using non-GLP screening protocols or GLP and OECD compliant protocols. These include the Ames Test (screening or OECD 471 compliant), in vitro (screening or OECD 487 compliant) micronucleus test, the GreenScreen HC™ assay, or the in vitro Comet assay.
Cyprotex now offer services to analyse 3D microtissue or spheroid models using multi-parametric high content imaging or by assessing ATP content.
Our in vitro ADME and DMPK services include in vitro metabolism, in vitro permeability and transporters, solubility and physicochemical properties, in vitro protein binding and PK and bioanalysis - Highly reproducible, accurate data - validated and used by over 1500 clients from the pharmaceutical, biotechnology, agrochemical, tobacco, cosmetics, health care companies and academic and government organisations. - Delivery of data for core in vitro ADME screening and physicochemical assays is within 10 working days to fit in with the make-test timelines in drug discovery. A number of different reporting options are available. - Highly cost effective due to our emphasis on high throughput engineering for key in vitro screening assays. - Attention to good quality customer care, with highly trained Principal Scientists on hand to explain results and suggest the most appropriate experimental strategy. - Flexibility - studies can be tailored to our customers’ specific requirements. - Regulations - our ADME services maintain and comply with regulatory guidelines providing constant confidence in the data. Our facility has passed evaluations by a range of different organisations and companies from a variety of differing industries, including government agencies: All now routinely use our services to provide support to their programs.
Cytochrome P450 Time Dependent Inhibition (kinact/KI)
Understand the potential drug-drug interaction (DDI) liability of your compounds by using our human cytochrome P450 (CYP) time dependent inhibition (TDI) assays for a range of isoforms.
TDI of CYP, often caused by an irreversible or quasi-irreversible interaction, can lead to clinically relevant DDI or non-linear pharmacokinetics of a drug. In addition, these interactions may indicate reactive metabolite formation which is also associated with toxicity via covalent binding to cellular macromolecules.
Characterisation of the kinact (maximal inactivation) and KI (concentration at 50% kinact) parameters is frequently performed during drug development to evaluate risk of TDI and decide if a clinical interaction study is required.
Our range of CYP TDI services form part of our portfolio of in vitro ADME services. We deliver consistent and high quality data with the flexibility to adapt protocols based on specific customer requirements.
Microsomal Binding Assay
Use our microsomal binding assay to improve your prediction of in vivo pharmacokinetics and drug-drug interactions (DDI) by correcting for the extent of binding to microsomes.
Drug that is bound to microsomes is unavailable for direct interaction with drug metabolising enzymes. Correcting for non-specific microsomal binding in the in vitro microsomal stability assays can improve the accuracy of the prediction of in vivo metabolic clearance. Knowledge of microsomal binding is also important for the prediction of in vivo drug-drug interactions (DDI).
The microsomal binding assay forms part of Cyprotex's in vitro ADME screening services. We deliver consistent and high quality data with cost-efficiency that comes from a highly automated approach.
UGT Inhibition IC50 Determination
MAO Inhibition (IC50) Determination
Cytochrome P450 Time Dependent Inhibition Single Point
Cytochrome P450 Time Dependent Inhibition IC50 Shift
Cytochrome P450 Inhibition (IC50)
Cytochrome P450 (CYP) Reaction Phenotyping
Plasma Stability Assay
Monoamine Oxidase (MAO) Reaction Phenotyping
Low Clearance HµREL® Co-Culture Assay
Hepatocyte Stability Assay
S9 Metabolic Stability Assay
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