• in-vitro-biology-(22)

in vitro Screening Services

In vitro Screening Center

In Vitro Screening Center is designed to help advance novel test articles from initial conception to clinical testing as soon as possible. We offer a broad range of high quality services to support drug discovery programs at different phases, covering HTS, primary, secondary/cellular, target class focused screening, and selectivity and liability screening. The core competence of in vitro screening function is disease/target biology and assay development expertise supported by state-of-the-art technology platforms. A team of well-trained scientists help characterize compounds by providing high quality data in a cost-effective manner. in vitro Screening Services can be done independently or as part of integrated services together with Chemistry, DMPK and Pharmacology.

In addition, In Vitro Screening Center is equipped with the world-class compound management system. The dedicated CM team in conjunction with an informatics team is experienced in storing, achieving and handling compounds in either solid or solution. Our service spans from compound solubilization to source or assay ready plate preparation, to support in vitro screening or other drug discovery functional groups. The rigorous QC criteria and standard workflow ensure high quality of compound and efficiency of delivery.

Compound management’s offering includes: 

Compound storage and management:

  • Storage conditions: Temperature and humidity controlled environments, including RT desiccators or -20 Freezer
  • Containers: 1-D barcoded glass vial, 2-D barcoded matrix tube or 96/384-well plate
  • Operation system: Mosaic or CMS (home-made Compound Management System)

Compound solubilization and reformatting:

  • Compound dry dispensing to1-D barcoded glass vial or 2-D barcoded matrix tube
  • Compound solubilization in 1-D barcoded glass vial or 2-D barcoded matrix tube
  • Compound solubility testing (e.g. turbidity meter)
  • Compound reformatting from 2-D barcoded matrix tube to 96 or 384 well plate; or from 96-well plate to 384-well plate

Compound source plate preparation

  • One-time dilution or serial dilution with different strategy to save compounds
  • Employ 8-/96/384-channel liquid handler for compound cherry-pick and dilution
  • Employ acoustic technology to generate serial dilutions
  • Employ acoustic technology to generate serial dilutions for combination study

Target based screening platforms

Enzyme based screening:

  • Kinase screening: Motility shift assay (EZ reader), Ulight, HTRF, IMAP, FP, ADP-Glo; LC/MS/MS, cellular phospho-substrate detection
  • Other enzyme screening: IMAP,FP,FI (Fluoresence intensity), Colorimetric, LC/MS/MS
  • Biophysics screening: Thermo-shift assay; TR-FRET; Biacore (coming soon)

Ion channel based screening:

  • Voltage-gated or ligand-gated channels
  • FLIPRtetra-based functional screening
  • Patch-clamp based electrophysiology screening
  • Primary cell culture for electrophysiology recording
  • Ion channel based screening:

GPCR based screening:

  • Radioligand binding or GTPrS binding
  • cAMP detection by LANCE ultra or HTRF
  • Calcium flux by FLIPR
  • IP3 detection
  • ERK phosphorylation
  • Reporter gene based readout

Nuclear receptor based screening

  • Competitive binding or Co-activation/repressor
  • Binding assay: FP or TR-FRET
  • Reporter gene based detection from either transient or stable cell line overexpressing NR
  • TaqMan based gene level detection

Phenotypic based screening platforms

Oncology

  • Cancer cell panel screening
  • Cell proliferation (CellTiter Glo)
  • Combination studies
  • Long-term incubation studies
  • 3D Clonogenic assay
  • Apoptosis assay
  • Cell cycle analysis
  • Angiogenesis
  • Migration/invasion assay
  • Nuclear translocation assay
  • Target validation (shRNA, RNAi, Crispr-Cas9)
  • Characterization of cell/animal model (whole exome; RNAseq)
  • Drug-resistant cancer and lines based assays

Cancer cell line panel screening

  • All the cells confirmed by STR
  • Multiple readout
  • Single dose or dose response curve
  • Share the same cell resource with in vivo pharmacology

Immunology

  • Cytokine/Chemokine profiling
  • T cell activation/proliferation
  • B cell activation   
  • ADCC
  • Co-Culture (e.g.Immune cells with tumor cells)
  • PBMC assays
  • Human whole blood assays
  • Immune reporter cells or HEK293-derived reporter cells
  • GeneBlazer assay (JAK/STAT pathway)

Metabolic disease

  • GSIS (Intact islet/ Pancreatic beta cell)
  • 3T3-L1 differentiation
  • fatty acid synthesis assay
  • Glucose uptake
  • TG detection

CNS

  • Primary neuron culture
  • Stable cell line generation
  • Primary neuron recording
  • Brain slides recording (coming soon)
  • FLIPR or Electrophysiology based assay
  • Ligand-gated channel or voltage-gated channel
  • PD readout from brain sample or CSF

Selectivity and liability screening:

Kinase panel:

  • Over 300 kinase collected
  • Single dose or IC50 determination
  • Full-length/catalytic
  • Wild type and mutated version
  • Multiple readouts (Caliper, ADP-Glo etc)

GPCR panel:

  • Pharmacological related functional assay formats to choose from: calcium flux, cAMP,
  • Single dose or dose response for EC50 and IC50 determination
  • 36 selected targets relevant to clinical adverse drug reactions (ADR)
  • All cell lines produced in-house

Nuclear panel:

  • AR, ER, GR, PR, ROR,AhR, PXR FXR, CAR, etc. .
  • Reporter gene based detection from either transient or stable cell line overexpressing NR

Ion channel panel:

  • FLIPR or Electrophysiology based assay
  • Cardiovascular safety or CNS safety related ion channels (i.e. HERG, Nav1.5 etc.)
  • Glutamate, Potassium, Sodium, Calcium, Serotonin, GABA channels