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Drug Discovery at BioDuro (Icon)

Biology

Cutting edge technologies supporting a broad array of services including cell line & antibody reagent generation and target validation.

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Overview

BioDuro’s Discovery Biology team has extensive experience in assay development and compound screening using biochemical and cell-based phenotypic functional assays for all the major classes of drug targets. Operating in state-of-the-art laboratories, our scientists are fully equipped to provide a broad array of services that include in vitro biology support for small molecule drug discovery programs, cell line generation, recombinant protein production and customized biology services. These capabilities and services can be accessed as flexible stand-alone services on demand and can also be accessed as part of integrated drug discovery programs to meet the needs of different clients. For each project, we routinely generate project-relevant high-quality data in short turnaround times. By working together closely, our chemists, discovery biologists, and drug metabolism and pharmacokinetics (DMPK) scientists are able to provide BioDuro clients a range of flexible service models including integrated programs, full time employee (FTE) services or fee-for-services (FFS).

BioDuro Advantage

  • Personalized project management
  • Integrated discovery programs
  • Deep expertise in assay development and compound screening
  • Broad target class and therapeutic disease area expertise

Services

  • Development of biochemical and cell-based assays
  • Design and implementation of target-relevant assays (screening cascade)
  • Design and implement phenotypic functional assays and biomarker assays with high disease relevance and proximity to clinical end point
  • Compound primary screening, hit confirmation, IC50/EC50 testing
  • Medicinal chemistry compound SAR support & compound profiling
  • Counter screening and off target selectivity
  • Mode of actions studies
  • Protein and cell line production: either as stand-alone service or as part of collaborative programs
  • Other cellular and molecular biology services
 

Biochemical Assays

Enzymatic Assays

  • Kinase
  • Phosphatase
  • Protease
  • GTPase
  • Oxidase
  • Hydrolase
  • Carboxylase
  • Nucleotidase
  • DNA polymerase
  • Phosphohydrolyase
  • Nicotinamide
  • Phosphoribosyltransferase

GPCR membrane prep binding assays

  • 3H- labeled ligand binding assay
  • SPA assay
  • FP assay

Epigenetics targeted assays

  • Bromo domain containing protein binding partner assays
  • Protein arginine methyltransferase
  • Histone methyltransferase
  • Histone acetyltransferase
  • Histone lysine demethylase
 

Cellular Assays

Phenotypic Functional Assays

  • Immunology and Inflammation assays
  • Oncology assays
    • 2D- or 3D-CTG/MTT/CCK8/LDH/CyQuant/SRB/Caspase 3&7/PI-Annexin V/BrdU
    • Migration, Invasion
  • Cell lines, primary cells, hWB, PBMC, T cell, B cell, and other immune cells

Target Based Assays

  • Targets: GPCR, Enzymes, Ion Channel, Transporter, NHR, TF
  • cAMP and IP-1 assays
  • Calcium flux assays
  • Reporter gene assays (Luciferase, β-lac, GFP, β-gal, etc.)
  • Membrane potential and Thallium flux assays
  • Uptake assays
  • Ion Channel assays (80+ targets, Qpatch and manual patch clamp)
  • Comprehensive in vitro Proarrhythmia Assay (CiPA)

Protein Marker Based Assays

  • Secreted and intracellular pathway and markers detection
  • Western blot
  • Sandwich ELISA
  • In-Cell ELISA (ICE)
  • FACS
  • HTRF/TR-FRET
  • AlphaLISA/AlphaScreen
  • Cell lines, primary cell-based MOA studies (e.g. target occupancy)

Customized Biology Services

  • Gene expression assays:
    • RNA extraction and purification, qPCR
    • Protein extraction and purification, Western blot, IP, IHC/IF/FISH
  • Stable cell lines
  • Gene editing:
    • CRISPR-Cas
    • HiBiT cell line generation for PROTAC programs

IMMUNOLOGY & IMMUNO-ONCOLOGY

  • Immuno-Oncology
    • PBMC, T cell, B cell and NK cell isolation
    • T cell activation and proliferation assays
    • Immuno-phenotyping or biomarkers analysis with multi-color FACS
    • Antibody-dependent cell-mediated cytotoxicity (ADCC)
    • T-cell infiltration into 3D tumor cell spheroids
    • Immunocytes cytotoxicity to cancer cells
    • Syngeneic mouse models
    • Lymphocyte Activation
    • Immune/Cancer Mixed Culture
    • Natural Killer
    • PBMCs
    • ADCC
    • Cytotoxicity
    • Inflammatory response

ION CHANNELS

  • Voltage gated sodium channels
  • Voltage gated calcium channels
  • Potassium channels
  • TRP channels
  • Ligand gated ion channels

METABOLIC & LIPID DISEASES

  • In vitro Assays for Metabolic & Lipid Diseases
    • Phenotypic Functional Assays
      • Primary hepatocyte isolation
      • Adipocyte differentiation
      • Lipogenesis assay (3H-Acetate)
      • Glucose uptake (colorimetric)
      • FA uptake (fluorometric)
      • Lipase activity assay
      • Beta-Oxidation (3-hydroxybutyric acid level)
    • Biomarker Analysis
      • Insulin level detection
      • Blood glucose, blood lipid level, Liver & kidney function analysis:
      • CHO, TG, HDL, LDL, BUN, CRE, ALT, AST
      • Fibrotic markers:
        • Collagen type 1a, 3a levels
        • TGF-b expression levels
        • Hydroxyproline levels
        • SMA-a levels
  • NAFLD/NASH Models
 

Kinase Assay Panels

  • For any kinases that are commercially available or can be produced recombinantly in-house, we can set up the enzymatic assay within a short time frame in either HTRF format (ready for > 160 kinases) or ADP-Glo format
  • Measurement of Kinact/Ki for covalent inhibitors
  • One-stop service with comprehensive assays to support kinase programs, with examples as below:

JAK family

  • Biochemical kinase activity assays for all JAK family members (JAK1-3, Tyk2, SYK)
  • Pseudo-kinase (JH2) binding assays for Tyk2 and JAK1
  • Cellular functional assays for all JAK family members (JAK1-3, Tyk2, SYK)

FGFR family

  • Biochemical assays for wild-type FGFR1, FGFR2, FGFR3, FGFR4, and FGFR2 (V564I), FGFR3 (V555M), FGFR4 (V550L), FGFR4 (V550M) mutants
  • Cellular functional assays for FGFR family members
 

GENE-TO-PROTEIN Services

  • Proteins with high purity for drug screening, SPR and crystallography
  • From pilot expression to scale-up production (10-15L)

Construct design & gene cloning

  • His, MBP, Strep, GST, SUMO, Flag tag, etc.
  • AviTag to produce biotinylated protein

Protein expression

  • E. coli expression system
  • Baculovirus Expression System (Sf9, High Five)
  • Mammalian cell Expression System (Expi293, ExpiCHO)

Protein purification

  • Affinity chromatography
  • SEC (Gel filtration)
  • IEX (e.g. HiTrapQ HP)

Protein characterization

  • Protein purity – SDS-PAGE, analytical HPLC
  • Protein homogeneity and aggregation states – DLS
  • Protein MW, modification, etc. – LC-MS
 

ASSAY PLATFORMS & TECHNOLOGIES

Assay Detection Formats

  • Fluorescence, absorbance, luminescence, FP, TR-FRET, HTRF, LANCE, Alpha
  • Filter binding, SPA and other radiometric assays
  • LC/MS
  • SPR
  • FLIPR
  • WB, ELISA
  • FACS and CBA multiplex

PROTAC

  • HiBiT cell line generation using CRISPR-Cas 9 technology and evaluation of PROTAC compounds in HiBiT cells
  • NanoBRET for target engagement, ternary complex formation and target protein ubiquitination evaluation

COVID19 ASSAYS

  • Pseudo-virus entry assay
  • Main protease (3CL Mpro) FRET-based biochemical assay
  • Papain-like protease (PLpro) fluorescence assay
  • TR-FRET based ACE2/RBD binding assay
  • SPR based binding assay

Key Instruments

  • Readers and Detection
    • EnVision, Enspire, TECAN Spark M10, SpectraMax
    • FLIPR Penta, Flexstation
    • TopCount, ABI 7500
    • Flow cytometers
    • CFX384 RT-PCR
    • ADDA High Speed – LC/MS
  • Liquid Handling
    • Multidrop Combi Dispenser
    • Apricot (Apricot Designs)
    • Agilent Bravo Automated Workstation
    • Echo Acoustic Liquid Handler (2.5nL-10μL, Labcyte)
  • Others
    • Full Range of standard equipment for cellular and molecular biology
 

BIOPHYSICS

Surface plasmon Resonance (SPR) is a core Biophysical technique used at BioDuro. We have a state-of-the-art SPR system, Biacore 8K (GE), at our Shanghai site.

SPR for Biologics

  • Affinity Maturation
  • Hot Spot Analysis/Stress Test
  • Fc Engineering
  • Anti-drug Antibodies (ADA)
  • Epitope Binning/Mapping
  • BsAb Construction
  • CAR-T scFv Screening and Selection
  • Antibody-Drug Conjugate (ADC)
  • Epitope Mapping
  • IND Package
  • Specificity Study
  • Cross-Reactivity
  • FcRn
  • FcγRs
  • C1Q

SPR for NCE

  • Compound binding affinity
  • Full binding kinetics and binding stoichiometry
  • Residence time
  • Fragment library screening
 

SAFETY PHARMACOLOGY

Safety assays

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