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Charles River - Discovery

US

Charles River utilizes a truly integrated approach to small molecule drug discovery, uniting all of the key disciplines required to achieve a program's goals in a single project team. As an experienced drug discovery organization, we are able to tailor project resources to meet the client's specific needs, integrating chemistry, physical sciences, CADD, biology, structural biology, ADMET/PK and disease models as required.

Charles River - Discovery has not listed any services.

GEM Colony Care
Genetically Engineered Mouse Colony Care
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Transgenic Breeding and Genotyping
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Adventitious Agent Testing
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Transgenic Animal Colony Management
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Drug Discovery Consulting
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Transgenic Animal Model Development
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Multiomics
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In vivo Toxicity Testing
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PK/PD/TK Data Analysis
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In vitro Immunotoxicity Testing
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In vivo Biosafety Testing
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In vitro Biosafety Testing
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Alzheimer's Disease Animal Models
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Rodent Breeding
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Biochemical Compound Screening
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The Charles River assay development and screening department offers a unique combination of target class and cell biology expertise together with state-of-the-art instrumentation to provide services tailored to your requirements.

We provide a collaborative environment and work closely with our teams in medicinal chemistry,... Show more »

The Charles River assay development and screening department offers a unique combination of target class and cell biology expertise together with state-of-the-art instrumentation to provide services tailored to your requirements.

We provide a collaborative environment and work closely with our teams in medicinal chemistry, ADME, structural biology and fragment-based drug discovery to deliver within challenging timelines.

Charles River has a range of orthogonal approaches that can deliver high-quality, validated hit compounds for your drug discovery project. These approaches can be applied in parallel or individually, depending on the nature of the project and the resources available. Our highly experienced teams regularly evaluate early-stage programs and will advise you concerning the best strategy for successful progression to hit-to-lead studies.

Hit Identification Approaches
High-throughput screening
Fragment screening
Virtual screening
Medicinal chemistry knowledge-based design

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Cell-Based Compound Screening
Price on request

The Charles River assay development and screening department offers a unique combination of target class and cell biology expertise together with state-of-the-art instrumentation to provide services tailored to your requirements.

We provide a collaborative environment and work closely with our teams in medicinal chemistry,... Show more »

The Charles River assay development and screening department offers a unique combination of target class and cell biology expertise together with state-of-the-art instrumentation to provide services tailored to your requirements.

We provide a collaborative environment and work closely with our teams in medicinal chemistry, ADME, structural biology and fragment-based drug discovery to deliver within challenging timelines.

Charles River has a range of orthogonal approaches that can deliver high-quality, validated hit compounds for your drug discovery project. These approaches can be applied in parallel or individually, depending on the nature of the project and the resources available. Our highly experienced teams regularly evaluate early-stage programs and will advise you concerning the best strategy for successful progression to hit-to-lead studies.

Hit Identification Approaches
High-throughput screening
Fragment screening
Virtual screening
Medicinal chemistry knowledge-based design

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Flow Cytometry
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Patient Derived Xenograft (PDX) Models
Patient-Derived Xenograft
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see full database at www.oncotest.com

see full database at www.oncotest.com

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CAR-T Cell Therapy Development
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Animal Housing and Maintenance
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Environmental Monitoring
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Environmental monitoring provides a proactive approach to identifying and excluding harmful factors that may affect the health of your animal colonies. Our professional staff members will work with to you develop a customized program for your facility utilizing microbiological or PCR testing methods.

Environmental monitoring provides a proactive approach to identifying and excluding harmful factors that may affect the health of your animal colonies. Our professional staff members will work with to you develop a customized program for your facility utilizing microbiological or PCR testing methods.

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Solubility and Dissolution Testing
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Charles River can measure the solubility, dissolution and stability of compounds under a variety of conditions. These data, together with Caco-2 permeability measurements produced by in vitro ADME screening, can be used to provide an early Biopharmaceutics Classification System (BCS) class for a compound.

Services
Kinetic... Show more »

Charles River can measure the solubility, dissolution and stability of compounds under a variety of conditions. These data, together with Caco-2 permeability measurements produced by in vitro ADME screening, can be used to provide an early Biopharmaceutics Classification System (BCS) class for a compound.

Services
Kinetic solubility measurement
Thermodynamic solubility measurement
pH solubility measurement
Solubility/Stability measurements in lung, gastric and intestinal fluid mimetics
BCS classification in conjunction with Caco-2 permeability measurements
Dissolution of API and early IMP formulations (paddle and flow-through)

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Drug Mechanism of Action Studies
Mechanism of Action Studies
Price on request

Charles River uses its adenoviral technology to elucidate the mechanism of action of small molecules. By combining the compound of interest with knockdown or overexpression of candidate gene in the same phenotypic assay, we can start to elucidate the mechanism of action of the compound(s).
In addition, we are able to access our... Show more »

Charles River uses its adenoviral technology to elucidate the mechanism of action of small molecules. By combining the compound of interest with knockdown or overexpression of candidate gene in the same phenotypic assay, we can start to elucidate the mechanism of action of the compound(s).
In addition, we are able to access our other technologies to perform mode-of-action studies:

  • Use of our in-house chemogenomics database to predict candidate targets
  • Cross-screening of compounds of interest through panels of biochemical and cell-based assays linked by candidate pathways or candidate gene families
  • Biophysical assays to look for compound binding to candidate target proteins – SPR, size exclusion chromatography, X-ray crystallography
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Stable Cell Line Generation
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Charles River has extensive experience in generating stable cell lines for high-throughput screening and compound profiling. We offer a customized service, starting with stable expression of single proteins through to stable co-expression of multiple protein subunits.

You can also access a range of validated assays, in addition... Show more »

Charles River has extensive experience in generating stable cell lines for high-throughput screening and compound profiling. We offer a customized service, starting with stable expression of single proteins through to stable co-expression of multiple protein subunits.

You can also access a range of validated assays, in addition to our assay development and validation service, with expression profile selected to suit specific assay formats.

Capabilities

  • Broad-spectrum molecular biology (gene cloning, mutagenesis, sequencing, vector construction and stable transfection)
  • FACS for assessment of expression levels and enrichment of cell populations
  • Large-scale cryopreservation of your cells (up to 1010 cells)
  • Large-scale transient expression using MaxCyte® STX™ allowing 40 million to 10 billion cells per transfection
  • Development of clonal transfected cell lines stably expressing ion channels and other membrane proteins with constitutive or inducible expression systems
  • Access to Charles River’s extensive portfolio of ion channel and GPCR cell lines
  • Validation of cell lines and assay protocols, including transfer of validated 'screen ready' assays to clients
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Protein Expression
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Charles River offers high-throughput production of high purity recombinant proteins for biological assays, biophysical studies and structural solutions. Working with a variety of protein expression systems, we are able to rapidly generate bespoke protein reagents to meet customer needs. Backed by years of expertise, we have... Show more »

Charles River offers high-throughput production of high purity recombinant proteins for biological assays, biophysical studies and structural solutions. Working with a variety of protein expression systems, we are able to rapidly generate bespoke protein reagents to meet customer needs. Backed by years of expertise, we have successfully produced of a variety of proteins for many structural studies.

Protein Production Services:

  • Construct design
  • Multi-parallel construct generation
  • Expression in E. coli, yeast, mammalian or baculovirus/insect cells
  • Fermentation and wave bags to 20 L scale
  • Automated protein purification
  • Purity of >95% routinely achieved
  • Labelled proteins for NMR
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Protein Crystallization
Price on request

The structural biology team at Charles River carries out high-resolution structure determination by X-ray crystallography to support both stand-alone and integrated drug discovery projects. We have access to both in-house and synchrotron data collection facilities to provide fast turnaround and high-throughput structure... Show more »

The structural biology team at Charles River carries out high-resolution structure determination by X-ray crystallography to support both stand-alone and integrated drug discovery projects. We have access to both in-house and synchrotron data collection facilities to provide fast turnaround and high-throughput structure determination (including fragment screening campaigns).

Integration of protein production, crystallization and structure solution allows for efficient streamlining of the structure determination process. The resulting structures, combined with the significant industrial design experience of our crystallographers and integrated with results from advanced biophysical assays, allow us to detail protein-ligand interactions at a structural, kinetic and thermodynamic level and provide insight to drug design projects.

  • Robotic nanoliter-scale screening and imaging
  • Screening with known ligands
  • Automated optimization of conditions for crystal growth
  • Co-crystallization or soaking of ligands
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Surface Plasmon Resonance (SPR)
Price on request

Surface Plasmon Resonance

  • Biacore 4000 for high-throughput hit identification
  • Biacore T200 with added sensitivity for kinetic profiling, mechanistic analysis and backup screening

Surface Plasmon Resonance

  • Biacore 4000 for high-throughput hit identification
  • Biacore T200 with added sensitivity for kinetic profiling, mechanistic analysis and backup screening
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Biacore
Biacore T-200
Biacore 4000
Analytical Chemistry Services
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Once compounds have been synthesized, they undergo purification, rigorous characterization, analysis and structural determinations as required using the latest equipment. We have the capability to perform nuclear magnetic resonance spectroscopy, mass spectrometry, infrared spectroscopy and single-crystal X-ray experiments.... Show more »

Once compounds have been synthesized, they undergo purification, rigorous characterization, analysis and structural determinations as required using the latest equipment. We have the capability to perform nuclear magnetic resonance spectroscopy, mass spectrometry, infrared spectroscopy and single-crystal X-ray experiments. High-throughput mass measurements are performed alongside high-throughput LC-MS analysis for structural and chemical purity determinations.

Analytical Chemistry Equipment

  • Waters/Agilent mass-directed autopurification
  • Waters Acquity UPC2 for supercritical fluid chromatography
  • Waters Thar SFC Prep 100 and Investigator systems
  • Waters Thar HT Resolution Analytical SFC-MS
  • Agilent 1200 chiral analytical HPLC
  • Gilson UV directed chiral HPLC purification system
  • High-throughput Acquity UPLC MS systems
  • Micromass Quattro Micro UPLC-MS-MS
  • Agilent 7820 GC plus Agilent 5975 MSD
  • Perkin Elmer SCIEX API5000
  • Waters XEVO QTOF accurate mass MS-MS system
  • Bruker Avance III HD 400 (x2), Avance DPX300, AV400, AVII 400 and Fourier 300 NMR spectrometers
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Waters Acquity UPC2
Waters Thar SFC-MS
Waters Thar SFC Prep 100
Agilent 1200 HPLC system
Gilson chiral HPLC system
Micromass Quattro Micro UPLC-MS-MS
Agilent 7820 GC
Agilent 5975 MSD
Perkin Elmer SCIEX API5000
Waters XEVO QTO
Bruker Avance III HD 400
Bruker Avance DPX300
Bruker Avance AV400
Bruker Avance AVII 400
Bruker Fourier 300
Medicinal Chemistry
Price on request

Our medicinal chemistry team is world-class, with many of our scientists bringing a wealth of experience from previous employment in the pharmaceutical and biotechnology industries. With our exposure to a wide range of therapeutic areas and collaborative working styles, we are well equipped to drive your program forward. We have... Show more »

Our medicinal chemistry team is world-class, with many of our scientists bringing a wealth of experience from previous employment in the pharmaceutical and biotechnology industries. With our exposure to a wide range of therapeutic areas and collaborative working styles, we are well equipped to drive your program forward. We have an enviable record of delivering 64 preclinical candidates to our partners, and the strength and consistency of our innovation is exemplified by inventorship on more than 290 patent applications filed by clients.

We provide integrated drug discovery services spanning hit identification, hit-to-lead and lead optimization, all complemented by synthetic, process and scale-up chemistry, computer-aided drug design, structural biology, assay development and screening, and comprehensive ADME and PK profiling.

Key Skills and Experience

  • Delivery of high-quality preclinical candidates
  • Broad therapeutic disease area expertise (e.g., respiratory, CNS, oncology, inflammation)
  • Significant experience working across all druggable gene family target classes
  • Problem-solving expertise and creativity
  • Interpretation of biological data
  • Understanding of physicochemical properties
  • Application of compound quality metrics
  • Development of structure-activity relationships
  • Removal of unwanted off-target activities
  • Optimization of ADME, PK and PK/PD profiles
  • Ability to execute patenting strategies
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Virtual Drug Discovery
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Collaborating with Charles River’s Computer-Aided Drug Design (CADD) group puts leading informatics, virtual screening and molecular modeling expertise at your fingertips. Our highly experienced team works closely with our colleagues in medicinal chemistry, screening and structural biology to support projects and also plays a... Show more »

Collaborating with Charles River’s Computer-Aided Drug Design (CADD) group puts leading informatics, virtual screening and molecular modeling expertise at your fingertips. Our highly experienced team works closely with our colleagues in medicinal chemistry, screening and structural biology to support projects and also plays a leading role in the design of our fragment and SoftFocus® libraries. Our CADD capabilities are available as part of integrated hit identification, hit expansion, hit-to-lead and lead optimization programs or as a stand-alone offering.

  • Structure-based drug design
  • Ligand-based drug design
  • Virtual screening
  • Protein modeling
  • QSAR modeling
  • Screening library design and subset selection
  • Design of fragment and SoftFocus® libraries
  • HTS data triage
  • Chemo- and bio-informatics
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Toxicology
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Non-GLP Toxicology
Charles River provides services in non-GLP bioavailability, pharmacokinetics and toxicity analysis in addition to in vitro assays designed to assess the cytotoxic, genotoxic and cardiotoxic potential of candidate molecules.

Acute Toxicity Testing

  • Timed dosing and sampling
  • Tissue and/or organ... Show more »

Non-GLP Toxicology
Charles River provides services in non-GLP bioavailability, pharmacokinetics and toxicity analysis in addition to in vitro assays designed to assess the cytotoxic, genotoxic and cardiotoxic potential of candidate molecules.

Acute Toxicity Testing

  • Timed dosing and sampling
  • Tissue and/or organ preservation
  • Plasma and/or serum sampling
  • Histology and pathology
  • CBC with differentials

In vitro Cytotoxicity Testing
- Cell viability: ATP and MTS endpoint
- Membrane integrity: LDH endpoint
- Apoptosis: caspase-3/7 endpoint

Genotoxicity Testing
- BlueScreen assay
- MicroAmes assay
- Micro in vitro micronucleus test

Skin Penetration Testing

  • Cardiotoxicity Testing
  • hERG channel blockade
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ADME and DMPK Studies
Drug Metabolism and Pharmacokinetics
Price on request

Charles River offers standard and custom in vivo and in vitro DMPK services utilizing a range of administration routes, dosing regimens and species. A dedicated study director will guide you from formulation to data delivery with a study protocol designed for your program and needs. Our quality studies include expert scientific... Show more »

Charles River offers standard and custom in vivo and in vitro DMPK services utilizing a range of administration routes, dosing regimens and species. A dedicated study director will guide you from formulation to data delivery with a study protocol designed for your program and needs. Our quality studies include expert scientific consultation and a summary report that can be adapted to your own existing template or format. We also commit to rapid study timelines and competitive pricing.

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Custom Cell-Based Assays
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Human Primary Cellular Assays - PhenoFocus

PhenoFocus is a portfolio of over 100 complex human primary cell-based assays for screening in more than 20 different disease area indications. Using cells derived from tissue, blood or differentiated stem cells, these high-throughput assays accelerate drug discovery by delivering... Show more »

Human Primary Cellular Assays - PhenoFocus

PhenoFocus is a portfolio of over 100 complex human primary cell-based assays for screening in more than 20 different disease area indications. Using cells derived from tissue, blood or differentiated stem cells, these high-throughput assays accelerate drug discovery by delivering the right candidate in the most relevant biology.

As our understanding of the complex interplay of networks and pathways within cellular processes increases, the need for ways to screen compounds in the correct disease context also grows. Charles River has extensive experience screening in disease-relevant human primary cells with functional readouts in medium- and high-throughput.

We offer customized assay development and screening with readouts including high-content screening and multiparameter detection (HT-FACS, Luminex and Meso Scale Discovery). With quality systems applied throughout the process—from cell culture to data analysis—we deliver data you can trust.

Benefits:

  • 100 complex human primary cell assays for hit finding, target discovery and target validation
  • Cells derived from tissue, blood and differentiated stem cells
  • Cells from healthy donors or donors with defined disease characteristics
  • High-content platforms with multiplexed readouts
  • Scientific expertise in over 25 human primary cell types and more than 20 disease indications
  • Mechanism of action studies using adenoviral SilenceSelect® and FLeXSelect® libraries
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Custom Biochemical Assay Development
Price on request

Charles River develops and executes more than 100 assays per year covering an extensive range of target classes. We have broad expertise in developing biochemical and cellular assays for:

  • Ion channels
  • Epigenetic protein targets
  • Kinases
  • G-protein coupled receptors (GPCRs)
  • Protein-protein interactions

Beyond the... Show more »

Charles River develops and executes more than 100 assays per year covering an extensive range of target classes. We have broad expertise in developing biochemical and cellular assays for:

  • Ion channels
  • Epigenetic protein targets
  • Kinases
  • G-protein coupled receptors (GPCRs)
  • Protein-protein interactions

Beyond the target family expertise, our scientists regularly develop assays for novel modes of actions to address pharmacological relevance.

Clients can access our assay development service or elect to transfer their own validated assays to us. We have developed disease-relevant assays in human primary cells for inflammatory diseases, bone and joint diseases, respiratory diseases, neurodegenerative diseases, obesity and diabetes, as well as oncology.

Key Technology Platforms

  • 96, 384 and 1536 densities
  • Capillary-based and automated pipetting instrumentation
  • Radioisotopic assays
  • Electrophysiology, including automated patch-clamp and conventional techniques
  • Multi-modal fluorescence and luminescence readouts
  • High-content, multi-parametric analysis
  • High-throughput plate imaging
  • Multi-array electrochemiluminescence detection
  • Label-free screening
  • Surface plasmon resonance
  • "Lab on a chip" microfluidic assays
  • Screening under Biosafety Level 2 containment
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Biomarker Discovery
Price on request

Novel Biomarker Identification

The identification and use of predictive biomarker assays has become an integral part of the drug discovery and development process. Charles River has broad expertise in biomarker identification and assay development across a range of therapeutic areas, including respiratory disease, oncology,... Show more »

Novel Biomarker Identification

The identification and use of predictive biomarker assays has become an integral part of the drug discovery and development process. Charles River has broad expertise in biomarker identification and assay development across a range of therapeutic areas, including respiratory disease, oncology, CNS and metabolic diseases.

Capabilities span the identification and validation of biomarkers and the development of quantitative assays in primary cells and disease tissue, pharmacodynamic and disease models, and as efficacy and translational medicine markers in the clinic. Our experience includes the translation of biomarker assays for use in the clinic for several client projects.

Example Readouts:

  • Proteomic markers
  • Genomic markers
  • Phosphoprotein markers
  • Epigenetic markers

Assay Technologies:

  • MesoScale for multiplexed immunoassay endpoints
  • FACS analysis
  • Mass spectrometry
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Protein Structure Determination
Price on request

Crystal Bank

Charles River has experience with many targets of pharmaceutical interest covering a range of gene families, including kinases (Ser/Thr and Tyr), phosphodiesterases, nuclear hormone receptors, and proteases such as deubiquitinases and other epigenetic targets.
Crystal Bank is a library of >75 proteins with... Show more »

Crystal Bank

Charles River has experience with many targets of pharmaceutical interest covering a range of gene families, including kinases (Ser/Thr and Tyr), phosphodiesterases, nuclear hormone receptors, and proteases such as deubiquitinases and other epigenetic targets.
Crystal Bank is a library of >75 proteins with known routes to structure, which can be used to speed up the analysis of your protein/ligand complexes by X-ray crystallography.

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Protein Biophysical Characterization
Price on request

Charles River provides biophysical techniques using tailored high-quality biological reagents to accelerate and deepen the understanding of compound-target interactions. These techniques range from simple thermal shift assays to more advanced techniques, such as surface plasmon resonance (SPR) measurements (using Biacore™... Show more »

Charles River provides biophysical techniques using tailored high-quality biological reagents to accelerate and deepen the understanding of compound-target interactions. These techniques range from simple thermal shift assays to more advanced techniques, such as surface plasmon resonance (SPR) measurements (using Biacore™ instrumentation) that provide vital kinetic data on ligand binding to its target, and isothermal titration calorimetry (ITC) studies that generate important thermodynamic information about protein-ligand interactions.

We also have access to high-field NMR and mass spectrometry to further our expert analysis of mode of action studies and protein-protein or protein-ligand interactions.

Biophysical Techniques
Thermal shift assay
Mass spectrometry
Isothermal titration calorimetry
Surface plasmon resonance
NMR
Crystallography

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In vitro ADME
Price on request

Charles River provides comprehensive ADME services, which can be accessed as part of an integrated drug discovery program or as a stand-alone offering. With extensive knowledge of in vitro ADME gained through working within drug discovery environments at both pharmaceutical and biotech companies, our ADME experts offer a... Show more »

Charles River provides comprehensive ADME services, which can be accessed as part of an integrated drug discovery program or as a stand-alone offering. With extensive knowledge of in vitro ADME gained through working within drug discovery environments at both pharmaceutical and biotech companies, our ADME experts offer a consultative approach, ensuring that the right experiments are performed at the right time.
Many of our in vitro assays have multiple formats available to suit the different stages of the drug discovery pipeline, allowing us to offer a flexible approach to our ADME services. Validated, SOP-controlled assays are available, in addition to assay protocols and final reports tailored to your specific needs. We are happy to discuss the adoption of your protocols for any assay of interest.

Physicochemical Properties
Kinetic solubility
Thermodynamic solubility
Lipophilicity
Chemical stability

Metabolic Stability
Microsomes (both lung and liver)
S9 fraction (intestinal, lung and liver)
Cryopreserved hepatocytes
P450 isoforms
UGT isoforms
Plasma
Blood
Simulated intestinal/gastric fluids

Drug-drug Interactions
CYP450 inhibition: fluorescence based
CYP450 inhibition: mass spectrometry based
Time-dependent CYP450 inhibition
CYP450 induction

Detailed Metabolic Studies
Metabolite identification
Reaction phenotyping
Reaction kinetics (Vmax, Km)

Distribution
Plasma protein binding
Blood partitioning
Caco-2 permeation studies
MDR1-MDCK effective efflux
BCRP-MDCK effective efflux
Pgp ATPase
Permeation studies
Brain tissue binding
Lung tissue binding

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In vivo PK/PD Studies
Price on request

In Vivo ADME
Whether you have one compound or a library of compounds requiring drug metabolism assessment, Charles River can design, conduct and interpret the in vivo pharmacokinetic/ADME components of your program as part of our streamlined non-GLP screening services.

Quick study initiation, multiple species, resident... Show more »

In Vivo ADME
Whether you have one compound or a library of compounds requiring drug metabolism assessment, Charles River can design, conduct and interpret the in vivo pharmacokinetic/ADME components of your program as part of our streamlined non-GLP screening services.

Quick study initiation, multiple species, resident animal colonies (with chronic surgical models included) and various dose regimens and administration routes, plus bioanalytical support, provide the necessary tools you need to rapidly identify and optimize potential drug candidates.

Services
Bioavailability
Biliary excretion
Mass balance
Tissue distribution
Bioequivalence
Dose ranging
Linearity
Proportionality
Single, multiple and cassette dosing
Metabolite profiling

Surgical Models
Vascular access ports
Chronic bile duct cannulation in nonrodent species
Intestinal cannulation
Portal vein cannulation
Cardiovascular telemetry

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Preclinical PK/PD Studies
in vivo Pharmacokinetics/Pharmacodynamics
Price on request

Charles River provides an integrated approach to PK studies where study directors act as the single point of contact and are engaged from formulation to data delivery. In select studies, reports can be issued within 4 days of compound dosing.

PK Screening:
Short lead time for pharmacokinetic study initiation
Timed dosing... Show more »

Charles River provides an integrated approach to PK studies where study directors act as the single point of contact and are engaged from formulation to data delivery. In select studies, reports can be issued within 4 days of compound dosing.

PK Screening:
Short lead time for pharmacokinetic study initiation
Timed dosing by various routes (PO, IV, IP, IM, SC, ICV, IN, IT, etc.)
Single agents, cassette dosing, repeat doses
Radiolabeled compound capabilities
Multiple sample time points over extended periods
Rodents – blood, urine, bile, CSF, tissue
Nonrodents
Formulation services
In-house pharmacy with extensive experience and a wide range of standard vehicle components

Analysis & Reporting
Samples analyzed by Charles River or returned to client
Watson™ and WinNonLin® utilized for PK analysis and reporting of standard PK parameters (Cmax, Tmax, AUC0-∞, AUClast, VZ, CL, T1/2, bioavailability)
Standard report templates are available and all data can be adapted to client’s needs/existing templates.

Pharmacodynamic Screening
Following PK screening, discovery research typically warrants the investigation of repeatable pharmacodynamic (PD) biomarkers in multiple species. Charles River routinely conducts in vivo screening studies that generate both PK and PD endpoints. Whether your program needs the background of genetically altered rodent models, a diet-induced phenotype or tissue-specific target engagement, we can provide the customized study designs you require.

Capabilities
Short lead time for study initiation
Timed dosing by various routes (PO, IV, IP, IM, SC, ICV, IN, IT, etc.)
Single agents, cassette dosing, repeat doses
Radiolabeled compound capabilities
Multiple sample time points over extended periods
Rodents – blood, urine, bile, CSF, tissue
Histology and pathology expertise
Nonrodents
Formulation services
In-house pharmacy with extensive experience and a wide range of standard vehicle components
Bioanalytical support
Samples analyzed by Charles River or returned to client

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Salt Screening
Price on request

Salt Screening
With a wide range of pharmaceutically acceptable salts available, the correct choice of salt form and method of production can be vital. Charles River can perform multiple salt screens to improve an API or IMP’s solid form characteristics, such as solubility/dissolution, stability (both chemical and polymorphic)... Show more »

Salt Screening
With a wide range of pharmaceutically acceptable salts available, the correct choice of salt form and method of production can be vital. Charles River can perform multiple salt screens to improve an API or IMP’s solid form characteristics, such as solubility/dissolution, stability (both chemical and polymorphic) and hygroscopicity. Salts are characterized using a variety of techniques and their solubility assessed, thus providing early directional data for the selection of the optimum salt. We take an adaptive approach to help you meet your goals in the shortest possible timelines.

With the ability to scale up salts in jacketed vessels from 250mL to 20L, Charles River can provide sufficient material for all pre-GMP work if required and liaise with third parties to ensure the correct solid form is produced. Appropriate documentation is provided to facilitate GLP services.

Characterization of Salts
Determination of optimum conditions for production of salt using metastable zone width properties
Thermodynamic solubility measured in a range of aqueous buffers
Dissolution rates assessed in a variety of biologically relevant media
Long-term stability trials under ICH guidelines
Forced degradation studies including light and solution stability assessment
In-house micronization and particle size determination to meet specified requirements

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Compound Identification and Characterization
Price on request

Charles River has a full suite of capabilities to provide chemical purity (including chiral purity) and structural elucidation on compounds, impurities and degradants. We have access both internally and externally to state-of-the-art technologies, including high-field and solid-state NMR, high-resolution MS-MS and X-ray... Show more »

Charles River has a full suite of capabilities to provide chemical purity (including chiral purity) and structural elucidation on compounds, impurities and degradants. We have access both internally and externally to state-of-the-art technologies, including high-field and solid-state NMR, high-resolution MS-MS and X-ray diffraction.

If required, compounds can also be characterized by IR or Raman spectroscopy and their optical rotation/circular dichroism determined. Elemental analysis and small molecule crystallography are also available via third parties.
The reports produced by Charles River are suitable for inclusion in an IMPD (Investigational Medicinal Product Dossier).

In house:

  • Two 400 MHz and two 300 MHz NMR instruments
  • 14 mass spectrometers
  • Agilent mass-directed autopurification system
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Physical Analysis Methods
Price on request

A full knowledge and understanding of the properties of a compound is essential in drug discovery. At Charles River, we can measure a wide variety of molecular properties in both the solid and the solution state to facilitate rapid development.

Physical Properties

  • LogP, pKa, logD
  • Melting points and other thermal events... Show more »

A full knowledge and understanding of the properties of a compound is essential in drug discovery. At Charles River, we can measure a wide variety of molecular properties in both the solid and the solution state to facilitate rapid development.

Physical Properties

  • LogP, pKa, logD
  • Melting points and other thermal events using DSC
  • Degradation using TGA and TGA-IR
  • Hygroscopicity using DVS
  • Particle size
  • Particle morphology using SEM
  • Toughness and hardness
  • Lactose blend performance using NGI technology
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Polymorphism Screening
Price on request

Polymorphism Screening
The importance of understanding and controlling the crystalline form produced cannot be overstated. The production of the incorrect polymorphic form can have an effect on a variety of parameters which will have an impact on the quality of your API.
Charles River has the ability to perform multiple... Show more »

Polymorphism Screening
The importance of understanding and controlling the crystalline form produced cannot be overstated. The production of the incorrect polymorphic form can have an effect on a variety of parameters which will have an impact on the quality of your API.
Charles River has the ability to perform multiple crystallization screens to investigate solid-state polymorphism. Using a variety of techniques, we aim to identify and characterize all relevant polymorphic forms as well as any hydrates or solvates of your API. Ultimately, our goal is to identify and recommend the most thermodynamically stable form under ambient conditions and provide you with information on how to obtain it.

Polymorphism Characterization
XRPD to obtain a fingerprint diffractogram
TGA and DSC to understand thermal behavior
Microscopy to assess crystal habit (optical or SEM as appropriate)
Hot-stage microscopy to correlate with events observed in TGA and DSC
GVS to assess hygroscopicity
UPLC™ and 1H NMR to assess chemical purity, structural integrity and residual solvent levels
Storage under ICH guidelines to assess stability
Thermodynamic solubility and kinetic dissolution rates in any relevant media
Single-crystal X-ray diffraction (on special request)

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High Content Screening
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High-Content Platform

Our high-content screening (HCS) platforms offer high-throughput screening and high-content profiling using standard cell models, human primary cells or disease-related cell lines. We develop assays for small molecule screening using our 850,000 compound collection and for RNAi screening using our... Show more »

High-Content Platform

Our high-content screening (HCS) platforms offer high-throughput screening and high-content profiling using standard cell models, human primary cells or disease-related cell lines. We develop assays for small molecule screening using our 850,000 compound collection and for RNAi screening using our proprietary adenoviral platform, SilenceSelect®.

The infrastructure available in-house at Charles River includes multiple GE InCell Analyzer 2200 instruments, GE InCellAnalyzer 6000, TTP LabTech Acumen Explorer™, BD Pathway™ 435, LI-COR Odyssey imager and 10 TB and 30 TB dedicated image servers.

Our extensive experience in high-throughput screening, in-house image analysis algorithm design and disease biology allows us to make the right selection of cell type and assay parameters before initiating HCS. Our expertise in assay development, image analysis and screening includes:

  • Anchorage independence (in 3D)
  • Apoptosis and cell death
  • Autophagy and protein aggregation
  • Cell motility and migration
  • Cytoskeletal rearrangements
  • Epigenetic modifications
  • Live imaging (e.g., Ca flux)
  • Marker expression
  • Neurite outgrowth
  • Protein acetylation and phosphorylation
  • Receptor internalization and degradation
  • Sub-cellular localization
  • Translocation of transcription factors
  • Viral replication
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Fragment Screening
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Charles River has extensive capabilities in fragment-based drug discovery (FBDD), offering access to expertise in screening, structural biology, and computational and medicinal chemistry. Our range of fragment libraries and orthogonal fragment screening technologies allows us to customize a fragment-based lead discovery solution... Show more »

Charles River has extensive capabilities in fragment-based drug discovery (FBDD), offering access to expertise in screening, structural biology, and computational and medicinal chemistry. Our range of fragment libraries and orthogonal fragment screening technologies allows us to customize a fragment-based lead discovery solution to a wide array of target types.

Our FBDD platform provides access to:

  • Orthogonal Screening Technologies - Technologies include thermal shift assay, surface plasmon resonance (SPR) using Biacore™ instrumentation, isothermal titration calorimetry (ITC), NMR, high-concentration biochemical assay and X-ray crystallography
  • Structural Biology - Experience in the development of structure routes to support FBDD; in-house X-ray facility and Crystal Bank of structures
    Unique
  • Fragment Library - 1,500 member core library, 500 member kinase focused set and 500 member 19F labelled set, all designed for fragment screening and rapid FBDD optimization of hits
  • Computational Chemistry - Proprietary fragment hit expansion techniques and fragment shape-based analysis tools
  • Medicinal Chemistry - Expertise in structure-based drug discovery and fragment hit optimization
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Integrated Drug Discovery
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Charles River utilizes a truly integrated approach to small molecule drug discovery, uniting all of the key disciplines required to achieve a program's goals in a single project team. As an experienced drug discovery organization, we are able to tailor project resources to meet the client's specific needs, integrating... Show more »

Charles River utilizes a truly integrated approach to small molecule drug discovery, uniting all of the key disciplines required to achieve a program's goals in a single project team. As an experienced drug discovery organization, we are able to tailor project resources to meet the client's specific needs, integrating chemistry, physical sciences, CADD, biology, structural biology, ADMET/PK and disease models as required.

  • Target Discovery
  • Hit Identification
  • Hit-to-Lead
  • Lead Optimization
  • Academic Engagement Initiative
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Liver Fibrosis Animal Models
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Liver Steatosis Animal Models
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Mouse
NASH (Non-Alcoholic Steatohepatitis)
Energy Dispersive Spectroscopy
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X-Ray Powder Diffraction
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X-ray crystallography
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The structural biology team at Charles River carries out high-resolution structure determination by X-ray crystallography to support both stand-alone and integrated drug discovery projects. We have access to both in-house and synchrotron data collection facilities to provide fast turnaround and high-throughput structure... Show more »

The structural biology team at Charles River carries out high-resolution structure determination by X-ray crystallography to support both stand-alone and integrated drug discovery projects. We have access to both in-house and synchrotron data collection facilities to provide fast turnaround and high-throughput structure determination (including fragment screening campaigns).
Integration of protein production, crystallization and structure solution allows for efficient streamlining of the structure determination process. The resulting structures, combined with the significant industrial design experience of our crystallographers and integrated with results from advanced biophysical assays, allow us to detail protein-ligand interactions at a structural, kinetic and thermodynamic level and provide insight to drug design projects.

  • In-house X-ray facility with synchrotron access
  • Crystal bank of structures
  • Electron density maps
  • Scaled and merged diffraction data
  • Complete atomic coordinates
  • Structure interpretation
  • Ligand binding analysis (where appropriate)
  • Advice on medicinal chemistry design (where appropriate)
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High Throughput Screening
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Charles River offers state-of-the-art screening platform technologies for the identification of hit compounds. Based on experience in cell line generation, the development of the most physiological assay system, the application to high-throughput screening (HTS) technologies and the screening of our library of 850,000 synthetic... Show more »

Charles River offers state-of-the-art screening platform technologies for the identification of hit compounds. Based on experience in cell line generation, the development of the most physiological assay system, the application to high-throughput screening (HTS) technologies and the screening of our library of 850,000 synthetic compounds, we have delivered validated hit compounds from more than 20 HTS campaigns per year.

Our HTS facility is supported by a team of 50 scientists with an average of 10 years of experience in HTS and hit finding technologies from the pharmaceutical industry. As a high-quality provider in this space, we are well-equipped and suitably experienced in addressing challenging targets and assay systems.

Our hardware and personnel in HTS are underpinned by a dedicated focus on quality of reagents, assays, data and compound integrity. Our ISO 9001 accreditation ensures that robust processes are in place to support effective and confidential data handling through IDBS, Titian and Dotmatics software suites.

We are also able to provide compound screening services for client libraries with a capacity of up to 1 million compounds in single compound format or up to 3 million in compressed formats, with capacity to store a copy of your library for multiple screening campaigns.

Hit Expansion
Our hit expansion process is a highly cost-effective way to further enlarge the pool of active compounds following a screen and to gain early structure-activity relationship (SAR) data.
By examining chemical motifs and scaffolds found to have activity in the primary screen, we can mine our extensive compound collection and select sets of related compounds for follow-on screening. This is an effective route to rapid identification of additional hits and new scaffolds, and to build SAR around existing hits. These additional compound sets are identified using 2D and 3D similarity and pharmacophore searching.

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Virology Testing
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UV-VIS Spectroscopy
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Imaging & Spectroscopy
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Transdermals/Transmucosals
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HPLC
High Performance Liquid Chromatography
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Gene Therapy & Testing Protocols
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Controlled Release Formulation
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Sterility testing
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Drug Formulation Development
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Stem Cell Lines
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Feasibility Studies
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Statistical Analysis
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Chemical Stability Testing
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Product Stability Testing
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Regulatory Affairs Consulting
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Radiotracers and Radiopharmaceuticals
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European QP
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Quality Assurance Solutions
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Process Validation
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Endotoxin Testing
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Drug Potency and Efficacy Testing
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Large Animal Models for Efficacy
The use of larger species in later-stage, non-GLP drug discovery is a crucial step when progressing your lead candidates towards the clinic. Whether being used for pharmacokinetic and safety translatability across species, or confirmation of target engagement and efficacy from prior rodent models,... Show more »

Large Animal Models for Efficacy
The use of larger species in later-stage, non-GLP drug discovery is a crucial step when progressing your lead candidates towards the clinic. Whether being used for pharmacokinetic and safety translatability across species, or confirmation of target engagement and efficacy from prior rodent models, a larger species can provide a key dataset for IND submission. Our Discovery Services group has decades of experience with a wide range of large animal models in locations that span the globe. We can perform the research needed in these models to shepherd your drug discovery program towards the clinic.

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Drug Development Consulting
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Drug Discovery
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Drug Preformulation
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De Novo Drug Design
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Drug Development
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Preclinical Efficacy Studies
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Preclinical Study Design
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PCR
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In vivo Pharmacology Studies
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Pharmacogenetic Testing/Pharmacogenomics
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Particle Analysis and Characterization
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Chemistry, Manufacturing and Controls
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Mycoplasma Testing
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Clinical Sample Analysis
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Microscopic Analysis
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Gas Chromatography (GC)
Gas Chromatography
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Microbiology Testing
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Method Validation
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Method development
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Biosimilars/Biobetters
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In vitro Metabolic Stability Assays
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Biomarker Research – Tissue Based
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Mass Spectrometry
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Native Mass Spectrometry

  • Label-free technology for detecting protein-ligand complexes in their native state
  • Highly sensitive and information rich (binding mode, affinity and stoichiometry)

Native Mass Spectrometry

  • Label-free technology for detecting protein-ligand complexes in their native state
  • Highly sensitive and information rich (binding mode, affinity and stoichiometry)
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Manufacturing, Vaccines
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Biopharmaceutical Process Development
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Manufacturing, Custom
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Biopharmaceutical Manufacturing
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Manufacturing, Clinical Trials Supply
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Biopharmaceutical Manufacturing
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Mammalian Cell Culture
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Bioanalytical Analysis LC/MS/MS
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Lot Release Testing
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Assay Development
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Hit to Lead and Lead Optimization
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Charles River has a range of orthogonal approaches that can deliver high-quality, validated hit compounds for your drug discovery project. These approaches can be applied in parallel or individually, depending on the nature of the project and the resources available. Our highly experienced teams regularly evaluate early-stage... Show more »

Charles River has a range of orthogonal approaches that can deliver high-quality, validated hit compounds for your drug discovery project. These approaches can be applied in parallel or individually, depending on the nature of the project and the resources available. Our highly experienced teams regularly evaluate early-stage programs and will advise you concerning the best strategy for successful progression to hit-to-lead studies.

Hit Identification Approaches:

  • High-throughput screening
  • Fragment screening
  • Virtual screening
  • Medicinal chemistry knowledge-based design

Charles River conducts hit-to-lead projects in an efficient cycle of rational design, synthesis and biological evaluation. Typically, multiple hit series are evaluated in parallel, with a view to establishing the scope for further optimization. One or two series are then selected for progression into lead optimization studies.
We will work closely with you to define the compound profile required, prioritizing compounds for detailed evaluation and interpreting results from a customized screening cascade including primary target and cellular activity together with ADME/PK assessment and target engagement biomarker assay development. Our medicinal chemists have an impressive track record of delivering high-quality lead series to our clients within agreed timelines across a broad range of target classes and therapeutic areas.

Hit-to-Lead Activities:

  • Design and synthesis of new analogues for rapid SAR determination
  • Increasing compound potency and selectivity
  • Improvement of drug-like properties
  • Applying CADD to generate binding hypotheses and to investigate SAR
  • Early assessment of ADME properties
  • Evaluation of target engagement biomarker assays
  • Ranking of hits or hit series for lead optimization

Lead optimization is a core strength within Charles River. We are able to consistently deliver high-quality, preclinical development candidates (63 since 2001) within industry standard timelines, including the data required to support progression into investigational new drug (IND) studies. A significant percentage of the 63 candidates identified have progressed to clinical proof-of-concept, illustrating their high quality. In addition, the first drug on the market resulting from a collaboration with Charles River's medicinal chemistry group was announced in July 2014.
Our efficiency is achieved through the integration of key disciplines, such as assay development and screening, computer-aided drug design, ADME/PK and pharmaceutical sciences, into project teams with many years of experience in tackling the problems associated with converting leads into candidates. An additional aid to efficient decision making during this phase of a project is the use of translational biomarkers, which are employed whenever possible.

We also have many years of experience in providing medicinal chemistry services in joint project teams with a variety of pharmaceutical and biotechnology companies.
This collaborative approach to our partners' drug discovery programs is reflected in patent applications (where our scientists appear as joint inventors on client projects) and in our publications. Wherever possible, we encourage our scientists to publish, present and defend posters, and present orally at conferences.

Lead Optimization Deliverables

  • Compounds with maximized potency and selectivity plus minimized toxicity
  • Compounds with evidence of target or pathway engagement in human systems
  • Human dose predictions
  • Patent filings
  • Generation of a preclinical candidate meeting agreed criteria
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IND/NDA Submission
Investigational New Drug/New Drug Application Submission
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Analytical Validation
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Animal Model in vivo Analyses
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Analytical Method Development
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In vivo Immunotoxicity Testing
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Immunobiology Services
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Accelerated Stability Testing
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Bioanalytical Assays
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Bioavailability Studies
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In vitro Disease Models
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Omics
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Structural Biology
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Pharmacology & Toxicology
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Chemistry and Materials
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Cell-Based Assays
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Animal Models of Disease
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Purification Services
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Chromatography
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Computational & Statistical Analysis
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Genotyping Services
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Biomarkers
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Product Development & Testing
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Formulation & Manufacturing
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CNS/Neurology Animal Models
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Hepatic Animal Models
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Spectrophotometry
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Animal Models and Studies
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Liquid Chromatography
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Nucleic Acid Services
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Patient Derived Xenograft (PDX)
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Microscopy
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Radiochemistry
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Project Management & Consulting Services
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Cell-Based Screening Methods
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Immunoassays
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Lead Identification and Validation
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Biomolecular Interaction Analysis
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Xenograft Models
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Protein Services
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Testing of Cell Lines
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Biochemistry & Molecular Biology
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Engineering & Devices
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Cell and Tissue Culture
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Experimental Design
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Genetic Engineering
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Clinical Research
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Biology
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Consumer Product Testing Services
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FDA approval process
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Clinical Sample Services
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In vitro Toxicity Testing
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Regulatory Affairs Services
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Manufacturing
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Specialized Cell-Based Assays
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Business & Legal Consulting
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Cell Lines
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Material Characterization Services
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Protein Characterization Services
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Cells and Tissues
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Bioanalysis
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Oncology Animal Models
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Spectroscopy
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Drug Discovery & Development
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Biochemical Assays
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Cytometry
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Lab and Facility Services
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Product Quality Control and Assurance
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Protein Purification and Quantification
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Process Development Services
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DNA
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Ask A Question Find what you're looking for? If not, you can ask this lab a question:
2018-01-02 14:14:27 UTC

Net Promoter Score of 9 received for Toxicology.

Additional Ratings: satisfaction with deliverable: 8, satisfaction with timeliness: 7.
2018-01-02 05:28:59 UTC

Net Promoter Score of 9 received for Mycoplasma Testing.

Additional Ratings: satisfaction with deliverable: 9, satisfaction with timeliness: 9.
January 2, 2018

Positive review received for Mycoplasma Testing:

"Consistent, reliable mycoplasma testing service with rapid turnaround time."

2017-09-11 22:13:12 UTC

Net Promoter Score of 10 received for Preclinical Efficacy Studies.

Additional Ratings: satisfaction with deliverable: 10, satisfaction with timeliness: 10.
2017-05-30 20:16:03 UTC

Net Promoter Score of 10 received for Mycoplasma Testing.

Additional Ratings: satisfaction with deliverable: 10, satisfaction with timeliness: 10.

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