PROTAC®

Synthesis, Analysis, Purification and DMPK

  • We have 900+ chemists with considerable experiences in the linkers, E3 ligase ligand and target protein ligand synthesis since 2016
  • >60 clients/collaborations
  • >50 methods of Prep-HPLC and chiral-SFC for purification
  • Efficient in-vitro/in-vivo testing by WuXi DMPK
  • Experienced in versatile linkers synthesis, 100+ are readily available
  • Novel linker synthesis by high productivity, quality, speed, and reliability PROTAC ®  Platform
  • Experienced in CRBN/VHL/IAP/MDM2 and novel E3 ligase ligands synthesis, >30 CRBN/VHL ligands are readily available
  • 30 series of target protein ligands coupled with various linkers
PROTAC

Traditional FFS

From mg to hundreds of kg

> 20,000 compounds synthesized

> 90% on-time delivery

Library

> 100 libraries finished

1~5 step parallel synthesis

2~4 weeks of turn-around time

PROTAC ® Molecular Bank

  • A modular platform: More efficient PROTAC®synthesis
  • Customized PROTAC®: From mg scale to 200+ kg
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Linkers: Most frequently used linkers, e.g. PEG, alkyl, ”clickable”, and rigid linkers

  • In-stock compounds: More than 350 in-stock linkers or E3 ligase ligands based on literatures
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E3 ligase ligands: Common ligands are readily available, e.g. VHL, CRBN, cIAP, etc

Biochemical and Biophysics assays

WuXi AppTec in vitro pharmacology platforms, synergized with WuXi AppTec powerful chemistry platform and featured with structural biology platform, provide comprehensive solutions supporting PROTAC drug Research & Development:

  • Biochemical and cellular assays
  • Biophysics assays for kinetics/affinity characterization
  • Various assay formats with capability to run both end-point and real-time kinetic analysis in high throughput format

Biochemical assays

  • Binding/displacement
  • Purified protein
  • Labeled ligand/antibodies
  • Assay formats: FP, FRET or AlphaLISA

Biophysical assays

  • Kinetic binding of PROTAC-target binary complex
  • Kinetic binding of ternary complex
  • Cooperativity
  • Assay format: SPR and ITC

Cellular assay

  • Binary ligand binding (Target engagement and permeability studies)
  • Ternary complex detection (NanoBRET assay in cell and in lysate)
  • End point assays: HCS and WB

Binary/Ternary Complex Formation Assay Platform

  • Binary/ternary binding assays at formats on TR-FRET, AlphaScreen, Fluorescence Polarization (FP), radioactive assays, etc.
  • Biophysics approach with SPR (Biacore 8K+) and thermo shift assays SPR assay measures the kinetics of binary/ternary complex formation and provides rationale for preferred-ternary-complex-formation in PROTAC design and. optimization.