Bifunctional Molecules

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 ®1  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
targeted protein degraders and degradation, PROTAC, bifunctional molecules, molecular glues
PROTAC, bifunctional molecules, molecular glues, targeted protein degradation, TPD

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

Readily available, in stock collection of linkers and E3 ligands

  • A modular platform: More efficient synthesis of bifunctional molecules
  • Customized synthesis : From mg scale to 200+ kg
linkers, bifunctional molecules

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
E3 ligase ligands, bifunctional molecules, targeted protein degradation, TPD

E3 ligase ligands: Common ligands in stock readily available, e.g. VHL, CRBN, cIAP, etc

Biochemical and Biophysics assays

WuXi AppTec biology, chemistry and structural biology platforms provide comprehensive solutions to support protein degradation drug discovery research.

biochemical and biophysics assays for bifunctional molecules
  • 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 bifunctional molecules-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 bifunctional molecules design and optimization.

1 PROTAC® is a registered trademark of Arvinas Operations, Inc., and is used under license