High Content Platform

Overview

Cell-based functional bioassays of bio-relevant activities of enzymes, receptors, and signaling molecules and pathways. Integrated multi-parameter analysis for customized specific needs.

Applications

  • Targeted Drug Screening
  • Target-Hit Search
  • Hit to Lead Identification
  • Lead Optimization
  • Drug Mechanism of Actions
  • Drug Kinetics
  • Drug Cytotoxicity

Specific Assays: 2D/3D/4D Image Based Quantitative and Semi-Quantitative Functional Bioassays

  • Cell Proliferation Assay (growth rate, doubling time, viability, etc.)
  • Cell Death Assay (apoptosis, necrosis, autophagy)
  • Cell Cycle Assay (cell cycle phases, mitosis, quiescence, senescence)
  • Subcellular Localization & Translocation Assay (endocytosis, exocytosis, nuclear/cytosol, nuclear structure)
  • Subcellular Organelle Function Assay (mitochondria, Golgi body, endoplasmic reticulum, etc.)
  • Membrane Integrity and Function Analysis
  • Kinase and Signal Transduction Analysis
  • Cell-Cell Interaction Analysis
  • Cell Sub-Population Analysis and Enrichment
  • Cytoskeleton and Extracellular Matrix Analysis
  • Cell Motility, Invasion, and Chemotaxis Assay
  • Oxidative Stress and Cellular Response Analysis
  • DNA and Chromosome Damage, and Genetic Instability Analysis
  • Epigenetic Modification Analysis
  • Transcription Activation and Gene Expression Analysis
  • DNA/Protein Synthesis and Degradation Analysis
  • Protein-Protein, Protein-DNA, Protein-RNA Interaction Analysis
  • Protein Post-Translational Modification and Activation Analysis
  • Customized Services – Please contact us for your special needs.

Cellular Assays

2D/3D Cell Culture

Cell Engineering Service

  • Gene knock-out, Allele-specific genome editing, Inducible gene knock-down
  • Drug resistant cell line generation, Stable cell line generation, Phenotypic analysis (Key technology: CRISPR/Cas9, Lentiviral system)

CRISPR/Cas9 Based Method for KO/KI Cell Line Generation

Target-based Mechanistic Assays

  • DNA, RNA, Protein level
  • Subcellular localization
  • Signaling pathway research
  • Cellular detection of protein phosphorylation
  • Protein-Protein interaction
  • Cell metabolite detection
  • Cell morphology and phenotype analysi

Potency Correlation of Protein-Protein Interaction

Cell Function

Cell viability/toxicityCell proliferationCell cycleCell motility/migrationCell apoptosis2D/3D Clonogenic assay

OrisTM Migration Assay

Transwell Migration Assay

3D Clonogenic Assay


Enzymes/Biochemical Assays

Overview

Enzyme/biochemical assays are essential tools to screen compounds that bind to target proteins with a defined mechanism. In recent years a large variety of enzyme/biochemical assays have been developed to discover and to optimize compounds that inhibit the activity of these targets.

As part of the WuXi Research Service Division (RSD), the Biology Unit is led by a group of leading scientists with significant experience in drug discovery.The RSD Biology Unit is dedicated to providing open access and integrated platforms for supporting plate-based screening services, including HTS, hit identification, lead optimization, selectivity screening and early safety profiling, up to drug candidate selection.

Assay Development

  • Strong expertise relating to enzymology in drug discovery.
  • Capabilities for assay development on diverse targets: kinase, phosphatase, ATPase, polymerase, dehydrogenase/reductase, protease, epigenetic enzymes (HMT, KDM, HDAC, Bromodomain), ligand-receptor (protein) binding and PPI.
  • Example of assay development

Assay Formats

  • End-point assay & continuous assays
  • Plate-based screening platform
  • Major assay platforms: TR-FRET, FP, ADP-Glo, Z-Lyte , ELISA, absorbance, LC/MS

Compound Profiling

  • Weekly screening service to provide clients high quality, timely data, with the ability to solve problems and communicate effectively 
  • Potency measurements across multiple target classes (IC50, Ki)

Inhibitor Characterization

  • Compound evaluation, as a part of SAR, to understand MOA of inhibitors, including mechanism of inhibition, time-dependent inhibition and reversibility of inhibition
  • Example of studying mechanism of inhibition

GPCR, Transporter and NHR

GPCR Assays

G-protein coupled receptors (GPCRs) form the largest class of cell-surface receptors. There are ~ 800 GPCRs overall, and as such this target class is very important in drug discovery. Currently around, ~ 35% of all drugs approved by the FDA act at 108 unique GPCRs1.

1. Hauser et al. (2017). Trends in GPCR drug discovery: New agents, targets and indications Nature Reviews Drug Discovery 16(12): 829–842

Comprehensive In Vitro GPCR Services

  • Compound profiling:
    • Medchem programs
    • R&D programs: MOA
    • MTS and HTS
    • IND filing
  • Assay transfer, setup and/or development
  • Safety/off-target screening
  • Stable GPCR cell line generation

Diverse Platforms

Literature Dowload

  • Over 100 GPCR cell lines and corresponding assays in house (Read More)
  • GPCR assays for safety/off-target profiling (Read More)

Customized assays are routinely provided by scientific teams upon request.

Transporter and NHR (Nuclear Hormone Receptor) Assays

Radioligand binding and functional assays (Read More for Targets and Assays) 


High Throughput Screening

Identifying New Chemical Matter via High Throughput Screening (HTS)

State-of-the-art Equipment for HTS Support

Automation system

  • Tecan
  • POD and Echo
  • JANUS
  • BRAVO
  • Platemate Plus

Plate washers

  • Elx405 and Elx406
  • DropArray Washing StationPlate Sealers

Readers to support HTS

  • BD Biosciences Flow Cytometer with HTS mode
  • Envision (with stacker)
  • EnSpire2300
  • FlexStation III
  • Bioplex 200 Luminex
  • FLIPR and Hamammatsu
  • Topcount and Microbeta2
  • Q-Patch and Ion Works
  • Acumen and Odyssey (Li-COR)

HTS Compound Collection

  • Majority of the collection is semi-exclusive, non-commercially available
  • Selected from >550K compounds based on diversity, properties, PAINS* & Vacca-Reos# structural filters, reviewed by medicinal chemists, and Rule-of-5 Multi Parameter Optimization (MPO)
  • Total 167k compounds were collected and another 50k compounds expansion in progress
  • Arrayed in 384 plate ready for HTS
  • Stocks and powders available in China

HTS Collection (166K) – Property Distributions

WuXi HTS Case Study


Cancer Cell Panel & In Vitro Oncology Assays

Overview

We also offer a diverse in vitro screening panel of over 378 authenticated, well-validated human cancer cell lines across 21 organs/tissues. The cancer cell panel provides powerful tools for cancer research and drug discovery. Key features of the WuXi cancer cell panel include:

  • High quality cell banking system: mycoplasma-proof and STR verified
  • Single agent and combination compound screening for potency (% inhibition & IC50) and synergy (combination index CI)
  • Professional design with stringent quality control of study results
  • A database of cell growth curve and Standard of Care (SoC) validation data provides guidance for cell model selection
  • Fast study turnaround
  • A comprehensive range of functional assays

Large Scale Human Cancer Cell Lines for Cell Panel Services

A wide range of 378 human cancer cell lines is available for oncology drug discovery programs. The cell banking system is a two-tiered banking system with mycoplasma testing and STR validation. Established cell growth data and standard of care profiling enhance the quality of study. The table shows the distribution of 378 human cancer cell lines, sorted by the origins of derived organs/tissues.

Synergistic effects of Compound X with Ibrutinib in TMD8

Potency Correlation of Compounds (kinase assay & cell proliferation assay)


In Vitro Assays for Diabetes and Other Metabolic Diseases

In Vitro Assays for Diabetes

The WuXi Biology department has established a full package of in vitro assays and services to support:

  • Drug discovery programs
  • IND filing
  • Biosimilar equivalence assessment
  • Biosimilar product quality testing
  • Onsite inspection by CFDA

Comprehensive In Vitro Assay Platforms for Diabetes

Introduction and representative data brochure: Click for: WuXi Diabetes Service Brochure

In Vitro Assays for Other Metabolic Diseases

More assays for enzymes, receptors and other proteins associated with metabolic diseases:  Please click here to request information.


Ion Channel

Overview

Ion channels are important drug targets because they play a crucial role in controlling a very wide spectrum of physiological processes, and also ion channels are closely related to drug safety. WuXi AppTec Biology has been providing ion channel services for over 10 years. We offer a broad portfolio of functional assessments on ion channel at various drug discovery stages to accelerate your new drug discovery progress.  

Ion Channel Expression System Generation

  • Ion channel stable cell line generation
  • Ion channel BacMam expression system construction

Cardiac Safety Services

  • hERG and other cardiac channel testing: ion channel cardiac safety panel (CIPA compliant)
  • Stem cell derived cardiomyocyte studies with MEA

Click here for more information about the cardiac safety services. 

Ion Channel Drug Discovery Services

  • Compound screening: Ion channel HTS, support hit finding to lead optimization programmes
  • MOA studies for lead compounds: Conventional patch-clamp studies at cellular or tissue level, using stable cell lines expressing ion channels, native cells (dissociated DRG cells, primary cultured cortical or hippocampal neurons) and/or IPSC derived neurons or cardiomyocytes

Advanced Ion Channel Screening Capability and Capacity

  • Automated and manual patch-clamp instruments
  • Compound profiling | Technical platform:
    • Automated and conventional patch-clamp
    • FLIPR assays, ion channel HTS
  • Reagent generation
    • Ion channel stable cell line generation
    • Ion channel BacMam expression system construction

Examples

Sodium channel IV curve obtained with QPatch 

GABAA current recorded from primarily cultured hippocampal neurons with manual patch-clamp

Effects of Quinidine on human stem cell derived ventricular cardiomyocytes recorded on MEA


Radioactive Assays

WuXi Radioactive Laboratories

  • 120 square meters laboratories
  • 6 regular radioisotopes are licensed
    • 14C, 3H, 32P, 33P, 35S, 125I
  • Multiple radiometric counters to support different purpose of assay formats
    • Microbeta , TriCarb, Topcount and Gamma counter

Assay Targets and Platforms

Targets

Types of radioactive assay platforms

  • Filter binding assay
  • SPA (Scintillation Proximity Assay)/FlashPlate
  • Cellular uptake assay
  • Metabolic assay
  • High throughput screening (HTS)