C71zk5os3swnkychgseh conflu

Confluence Discovery Technologies

St. Louis, Missouri, US

Confluence is a Contract Research Organization providing Clients with 125+ Years of Drug R&D know-how and a proven track record having delivered 29 Phase I and 13 Phase II drug programs that resulted in 4 marketed drugs.

Confluence is located in the CORTEX Bioscience District adjacent to the Washington University School of Medicine in St. Louis, Missouri. Our highly trained scientists operate a state-of-the-art laboratory to support biochemistry and enzymology, cell and molecular biology, custom assay development, translational research, as well as computational and medicinal chemistry to ensure your project’s success.

The Confluence Team provides services from one time consultation to independently driving a drug discovery program.

Working closely with clients we assess project scope and needs while providing problem solving, strategy development and testing funnel design.

At project implementation we... Show more »

Confluence is a Contract Research Organization providing Clients with 125+ Years of Drug R&D know-how and a proven track record having delivered 29 Phase I and 13 Phase II drug programs that resulted in 4 marketed drugs.

Confluence is located in the CORTEX Bioscience District adjacent to the Washington University School of Medicine in St. Louis, Missouri. Our highly trained scientists operate a state-of-the-art laboratory to support biochemistry and enzymology, cell and molecular biology, custom assay development, translational research, as well as computational and medicinal chemistry to ensure your project’s success.

The Confluence Team provides services from one time consultation to independently driving a drug discovery program.

Working closely with clients we assess project scope and needs while providing problem solving, strategy development and testing funnel design.

At project implementation we collaborate as integral team members providing technical expertise and service along with frequent data updates and the flexibility to adjust to changing project needs.

Selected Publications

  1. Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, Rizzuti BJ, Sawyer PS, Perry BD, Brissette WH, McCurdy SP, Kudlacz EM, Conklyn MJ, Elliott EA, Koslov ER, Fisher MB, Strelevitz TJ, Yoon K, Whipple DA, Sun J, Munchhof MJ, Doty JL, Casavant JM, Blumenkopf TA, Hines M, Brown MF, Lillie BM, Subramanyam C, Shang-Poa C, Milici AJ, Beckius GE, Moyer JD, Su C, Woodworth TG, Gaweco AS, Beals CR, Littman BH, Fisher DA, Smith JF, Zagouras P, Magna HA, Saltarelli MJ, Johnson KS, Nelms LF, Des Etages SG, Hayes LS, Kawabata TT, Finco-Kent D, Baker DL, Larson M, Si MS, Paniagua R, Higgins J, Holm B, Reitz B, Zhou YJ, Morris RE, O'Shea JJ, Borie DC. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science. 2003. 302:875-8. 2.
  2. Milici AJ, Kudlacz EM, Audoly L, Zwillich S, Changelian P. Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis. Arthritis Res Ther. 2008.
  3. Morris DL, O. N. S., Devraj RV, Portanova JP, Gilles RW, Gross CJ, Curtiss SW, Komocsar WJ, Garner DS, Happa FA, Kraus LJ, Nikula KJ, Monahan JB, Selness SR, Galluppi GR, Shelvin KM, Kramer JA, Walker JK, Messing DM, Anderson DR, Mourey RJ, Whitley LO, Daniels JS, Yang JZ, Rowlands PC, Alden CL, Davis II JW, Sagartz J. Acute Lymphoid and Gastrointestinal Toxicity Induced by Selective p38 MAP Kinase and MAP Kinase-activated Protein Kinase-2 (MK2) Inhibitors in the Dog. Tox Pathol. 38, 606-613 (2010).
  4. Stephen J Mnich, Patrick M Blanner, Liangbiao G Hu, Alexander F Shaffer, Fernando A Happa, Shawn O'Neil, Okechukwu Ukairo, Dave Weiss, Eric Welsh, Chad Storer, Gabriel Mbalaviele, Hidenori Ichijo, Joseph B Monahan, Medora M Hardy and Hiroyuki Eda. Critical role for apoptosis signal-regulating kinase 1 in the development of inflammatory K/BxN serum-induced arthritis. International Immunopharmacology 10, 1170-1176 (2010).
  5. Hiroyuki Eda, Jian Zhang, Robert H Keith, Marshall Michener, David R Beidler and Joseph B Monahan. Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood. Cytokine 52, 215-220 (2010).
  6. Hiroyuki Eda, Hideaki Shimada, David R Beidler and Joseph B Monahan. Proinflammatory cytokines, IL-1b and TNF-a induce expression of interleukin-34 mRNA via JNK- and p44/42 MAPK-NF-kB pathway but not p38 pathway in osteoblasts. Rheumatology International. 31, 1525-1530 (2011).
  7. Shaun R Selness, Terri L Boehm, John K Walker, Balekudru Devadas, Richard C Durley, Ravi Kurumbail, Huey Shieh, Li Xing, Michael Hepperle, Paul V Rucker, Radhika Blevis-Bal, Rajesh V Devraj, Dean Messing, John F Schindler, Jeffrey Hirsch, Matthew Saabye, Sheri Bonar, Elizabeth Webb, Gary Anderson, Joseph B Monahan. Design, synthesis and activity of a potent, selective series of N-aryl pyridinone inhibitors of p38 kinase
 
Bioorganic and Medicinal Chemistry Letters. 21, 4059-65 (2011).
  8. Xing, Li; Devadas, Balekudru; Devraj, Rajesh V.; Selness, Shaun R.; Shieh, Huey; Walker, John K.; Mao, Michael; Messing, Dean; Samas, Brian; Yang, Jerry Z.; Anderson, Gary D.; Webb, Elizabeth G.; Monahan, Joseph B. Discovery and Characterization of Atropisomer PH- 797804, a p38 MAP Kinase Inhibitor, as a Clinical Drug Candidate. Chem Med Chem 7, 273-280 (2012).
  9. Elise Alspach, Kevin C. Flanagan, Xianmin Luo, Megan K. Ruhland, Hui Huang, Ermira Pazolli, Maureen J. Donlin, Timothy Marsh, David Piwnica-Worms, Joseph B. Monahan, Deborah H. Novack. Sandra S. McAllister and Sheila A. Stewart. P38MAPK Plays a Crucial Role in Stromal-Mediated Tumorigenesis. Cancer Discovery 4, 1-14 (2014).
  10. O’Connell BC, O’Callaghan K, Tillotson B, Douglas M, Hafeez N, West KA, Stern H, Ali JA, Changelian P, Fritz CC, Palombella VJ, McGovern K, Kutok JL. HSP90 Inhibition enhances antimitotic drug-induced mitotic arrest and cell death in preclinical models of non-small cell lung cancer. PLoS one 2014 Dec 26:9(12)
  11. Winkler DG, Faia KL, DiNitto JP, Ali JA, White KF, Brophy EE, Pink MM, Proctor JL, Lussier J, Martin CM, Hoyt JG, Tillotson B, Murphy EL, Lim AR, Thomas BD, Macdougall JR, Ren P, Liu Y, Li LS, Jessen KA, Fritz CC, Dunbar JL, Porter JR, Rommel C, Palombella VJ, Changelian PS, Kutok JL. PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.
  12. Kontzias A, Kotlyar A, Laurence A, Changelian P, O’Shea JJ. Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease. Curr Opin Pharmacol. 2012 Aug;12(4):464-70.
  13. SLAS 2015 Poster Presentation : 1029: A representative Kinase Selectivity Screening Panel to support drug discovery using the ADP-glo kinase activity format. Jeff Hirsch.
  14. SLAS 2015 Poster Presentation: 1045: Cancer Drug Discovery: High throughtput assays to evaluate cytostasis, cytotoxicity, apoptosis, chemoresistance and EMT of drug candidates. Heidi Hope.
  15. FASEB 2016 Poster and Presentation: Development and utilization of a target biomarker to evaluate ERK1/2 inhibition by BVD-523 (Ulixertinib) in preclinical and clinical cancer studies. Heidi Hope, Barry Burnett, Dean Welsch, Gary DeCrescenzo and Joseph Monahan.
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Cell-Based Assays
Price on request

CDT offers cellular assay development and screening.

CDT offers cellular assay development and screening.

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Biomarker Discovery
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Target, Mechanism and Disease Biomarkers identified, validated and executed across a wide range of targets, species and biological matrices.

Target, Mechanism and Disease Biomarkers identified, validated and executed across a wide range of targets, species and biological matrices.

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Human
Mouse
Rat
Dog
Immunology
Oncology
metabolic
inflammatory
Non-human primates
Kinase Assays
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We are leaders in mechanistic enzymology and focus on custom assay development. Screen your compound library in our sensitive, reliable assays that are easily scaled to meet your throughput needs. We can look at compound:target interaction, enzyme inhibitor mechanisms and direct binding kinetics.

We are leaders in mechanistic enzymology and focus on custom assay development. Screen your compound library in our sensitive, reliable assays that are easily scaled to meet your throughput needs. We can look at compound:target interaction, enzyme inhibitor mechanisms and direct binding kinetics.

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Drug Mechanism of Action Studies
Mechanism of Action Studies
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We have the expertise to evaluate the mechanisms of action studies by characterization of binding mechanisms (competitive, noncompetitive, uncompetitive, irreversible, slow tight binding and aggregate) and binding kinetics (time-dependence and steady-state). We also provide progress curve analysis.

We have the expertise to evaluate the mechanisms of action studies by characterization of binding mechanisms (competitive, noncompetitive, uncompetitive, irreversible, slow tight binding and aggregate) and binding kinetics (time-dependence and steady-state). We also provide progress curve analysis.

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Mechanism-Based (Irreversible) Inhibition Assays
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Our experienced team provides mechanism of inhibition studies, looking at competitive vs noncompetitive, uncompetitive, irreversible vs slow tight binding and aggregate (non drugable).

Our experienced team provides mechanism of inhibition studies, looking at competitive vs noncompetitive, uncompetitive, irreversible vs slow tight binding and aggregate (non drugable).

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Cytokine Release Assay
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Using multiplex technologies such as MSD and Luminex, CDT can measure secreted proteins, intracellular proteins and look at signaling pathways.

Using multiplex technologies such as MSD and Luminex, CDT can measure secreted proteins, intracellular proteins and look at signaling pathways.

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Human
Mouse
Rat
Dog
Cell biology
Flow cytometry
Health & Inflammation
Arthritis
assay development
Development
ELISA
Osteoarthritis (OA)
Luminex
western blot
Non-human primates
Human Whole Blood & PBMCs
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CDT provides whole blood and PBMC cytokine release assays.

CDT provides whole blood and PBMC cytokine release assays.

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Human
Mouse
Rat
Dog
Surface Plasmon Resonance (SPR)
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CDT offers SPR assays, using the Biacore 2000, to measure the binding affinity (Kd).

SPR Real Time Binding for

Therapeutic Ab:
- Quantitation of target affinity
- Determination of binding kinetics
- Evaluation of specificity
- Competition epitope mapping

Small Molecule Drug:
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CDT offers SPR assays, using the Biacore 2000, to measure the binding affinity (Kd).

SPR Real Time Binding for

Therapeutic Ab:
- Quantitation of target affinity
- Determination of binding kinetics
- Evaluation of specificity
- Competition epitope mapping

Small Molecule Drug:
- Determination of affinity to target: enzyme, receptor, other macromolecular target
- Binding kinetics
- Target specificity

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Hit to Lead and Lead Optimization
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CDT offers project management and provide strategy with critical milestones and timelines. We can design and implement a testing funnel with clear compound advancement criteria.

CDT offers project management and provide strategy with critical milestones and timelines. We can design and implement a testing funnel with clear compound advancement criteria.

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Immuno-oncology Assays
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CDT offers cytotoxic T cell killing assays (using mouse splenocytes). Using differential labeling of control and specific target cells, allows quantification of killing.

CDT offers cytotoxic T cell killing assays (using mouse splenocytes). Using differential labeling of control and specific target cells, allows quantification of killing.

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B Cell Activation Assay
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CDT offers the B cell activation assay in human Ramos B cell line.

CDT offers the B cell activation assay in human Ramos B cell line.

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T Cell Activation and Proliferation Assays
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T cell subsets are generated in vitro from naive lymphocytes or whole splenocytes when treated with appropriate antibodies and "skewing" cytokines.

T cell subsets are generated in vitro from naive lymphocytes or whole splenocytes when treated with appropriate antibodies and "skewing" cytokines.

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Inflammation Assays
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Inflammation is the hallmark of allergy, infectious diseases, and wound healing. It is a leading cause of mortality worldwide and is indicated in eight major disease areas including autoimmune diseases, cancer, cardiovascular diseases, diabetic complications, infectious diseases, metabolic disorder complications, neurological... Show more »

Inflammation is the hallmark of allergy, infectious diseases, and wound healing. It is a leading cause of mortality worldwide and is indicated in eight major disease areas including autoimmune diseases, cancer, cardiovascular diseases, diabetic complications, infectious diseases, metabolic disorder complications, neurological diseases, and pulmonary diseases.
CDT offers custom multiplex inflammation assays that can detect and quantify biomarkers of inflammation from the TNF superfamily proteins, IFN family proteins, Treg cytokines, and MMPs.

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Cell Signaling Analyses
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Cell signaling pathway analysis by ELISA, western blot, FACS, Luminx and MSD analysis.

Cell signaling pathway analysis by ELISA, western blot, FACS, Luminx and MSD analysis.

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ELISA
Enzyme-linked immunosorbent assay
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High-throughput 96-well format, custom designed or kit-based ELISAs. CDT can analyze serum, plasma, cell lysates, cell culture supernatants. We can measure cytokines, transcription factors, protein phosphorylation, histone acetylation etc.

High-throughput 96-well format, custom designed or kit-based ELISAs. CDT can analyze serum, plasma, cell lysates, cell culture supernatants. We can measure cytokines, transcription factors, protein phosphorylation, histone acetylation etc.

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ELISA
Human Primary Cell Isolation
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PBMC isolation and neutrophil isolation from human/rat whole blood

PBMC isolation and neutrophil isolation from human/rat whole blood

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Human
Rat
Assay Development
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CDT provides both enzyme and cellular assay development and screening. We work closely with our clients to understand their needs and set critical milestones and timelines.

CDT provides both enzyme and cellular assay development and screening. We work closely with our clients to understand their needs and set critical milestones and timelines.

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Transfection
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CDT offers transient transfection of mammalian cells in both adherent or suspension cell cultures.

CDT offers transient transfection of mammalian cells in both adherent or suspension cell cultures.

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Preclinical PK/PD Studies
in vivo Pharmacokinetics/Pharmacodynamics
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CDT provides PK/PD studies to support the early stages of the drug discovery process. Routes can be IV, oral gavage, tail vein etc.

CDT provides PK/PD studies to support the early stages of the drug discovery process. Routes can be IV, oral gavage, tail vein etc.

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Mouse
Rat
Flow Cytometry
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CDT offers FACS analysis for rapidly analyzing a large number of cells individually using light-scattering, fluorescence, and absorbance measurements.

CDT offers FACS analysis for rapidly analyzing a large number of cells individually using light-scattering, fluorescence, and absorbance measurements.

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Molecular Cloning
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CDT offers a broad range of custom cloning services at a reasonable cost. We offer essentially all recombinant DNA services, including gene synthesis, PCR cloning, plasmid vector design and construction.

CDT offers a broad range of custom cloning services at a reasonable cost. We offer essentially all recombinant DNA services, including gene synthesis, PCR cloning, plasmid vector design and construction.

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Drug Target Identification
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Industry leading enzymologists at CDT provide Drug:target assays, looking at binding kinetics (Kon and Koff).

Industry leading enzymologists at CDT provide Drug:target assays, looking at binding kinetics (Kon and Koff).

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qPCR
Quantitative PCR
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CDT provides services for RNA, miRNA, and DNA samples, including RNA/DNA extraction, RNA quality control and quantification and cDNA synthesis for quantitative-PCR; and QRT-PCR.

CDT provides services for RNA, miRNA, and DNA samples, including RNA/DNA extraction, RNA quality control and quantification and cDNA synthesis for quantitative-PCR; and QRT-PCR.

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Methyltransferase Assays
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Methylation of proteins, nucleic acids and oligosaccharides is an important post- translational regulatory event. CDT offers end-point or kinetic read options, which are ideal for determining mechanism of action, kinetics, and screening candidate compounds.

Methylation of proteins, nucleic acids and oligosaccharides is an important post- translational regulatory event. CDT offers end-point or kinetic read options, which are ideal for determining mechanism of action, kinetics, and screening candidate compounds.

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Computational Chemistry
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CDT offers Schrodinger enabled structure based drug design.

CDT offers Schrodinger enabled structure based drug design.

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Signaling Pathway Analysis
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CDT offers cell signaling pathway analysis by multiplexing, ELISAs and western blot.

CDT offers cell signaling pathway analysis by multiplexing, ELISAs and western blot.

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Toxicology
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CDT offers in vitro ADME/Tox assays. We also offer genetic toxicology, safety pharmacology and general toxicology.

CDT offers in vitro ADME/Tox assays. We also offer genetic toxicology, safety pharmacology and general toxicology.

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Protein Purification
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CDT offers protein purification for any small to mid-scale, non-GMP protein purification projects.

CDT offers protein purification for any small to mid-scale, non-GMP protein purification projects.

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Drug Target Validation
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CDT offers a broad range of services related to drug target validation such as pathway-based approach to target ID or validation.We also offer many services related to the identification and validation of relevant biomarkers and drug targets.

CDT offers a broad range of services related to drug target validation such as pathway-based approach to target ID or validation.We also offer many services related to the identification and validation of relevant biomarkers and drug targets.

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In vitro Oncology Models
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Isothermal Titration Calorimetry (ITC)
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FRET/BRET
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Rheumatoid Arthritis Animal Models
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Human Tumor Xenograft Models
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In vivo Protein Binding Assays
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ADME/DMPK Studies
Drug Metabolism and Pharmacokinetics
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Optical Microscopy
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Protein Quantification
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Cell and Tissue Culture
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Oncology Animal Models
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Immunology Animal Models
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Enzyme Assays
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Human Biospecimens
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Animal Models and Studies
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Protein Services
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Pharmacology & Toxicology
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Medicinal Chemistry
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Physical Analysis Methods
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Engineering
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Biomarkers
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Biospecimens
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Protein Purification and Quantification
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Immune Cell Assays
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Experimental Design
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Nucleic Acid Services
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Biochemical Assays
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Project Management, Consulting, & Support Services
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Animal Models of Disease
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Biomolecular Interaction Analysis
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Drug Discovery
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In vitro Disease Models
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Microscopy
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Human Primary Cells
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Transferase Assays
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Fluorescence-Based Microscopy
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Biology
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Xenograft Models
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Imaging & Spectroscopy
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Chemistry and Materials
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Lead Identification and Validation
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Inflammation Animal Models
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Immunoassays
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Biochemistry & Molecular Biology
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Functional & Cell Type Specific Assays
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Drug Discovery & Development
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PCR
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Bioanalysis
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Cells and Tissues
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DNA
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Cytometry
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2017-09-26 19:39:08 +0100

Net Promoter Score of 10 received for Human Whole Blood & PBMCs.

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

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