Protein Degraders

WuXi AppTec utilizes state-of-the-art techniques to support drug discovery teams focused on targeted protein degradation. Our services include a broad range of ligand-finding methods, such as DEL, fragment screening, ASMS, and virtual screening. We provide custom linker design and complex synthesis for new linkers and E3 ligase ligands. To support lead optimization efforts, our platform offers cell-based assays and advanced biophysical and biochemical methods for measuring binary/ternary complex formation and target ubiquitination/degradation.

Bifunctional Molecules: Synthesis, Analysis, Screening

  • More than 1,000 chemists with extensive experience in the synthesis of linkers, E3 ligase ligands, and target protein ligand synthesis since 2016
  • >200 methods of prep-HPLC and chiral-SFC for analysis and purification
  • Comprehensive in-vitro/in-vivo testing platform
  • Expertise in versatile linkers synthesis; 200+ linkers and E3 ligase ligands in stock; more than 1,000 diverse linkers successfully synthesized
  • Novel linker synthesis with high productivity, quality, speed
  • Deep experience in CRBN/VHL/IAP/MDM2 and novel E3 ligase ligand synthesis; 30+ CRBN/VHL ligands are readily available; >100 novel E3 ligase ligands
  • >60 series of target protein ligands pre-coupled with various linkers
  • >90,000 Targeted Protein Degraders successfully delivered
targeted protein degraders and degradation, PROTAC, bifunctional molecules, molecular glues
PROTAC, bifunctional molecules, molecular glues, targeted protein degradation, TPD

Readily available, in stock collection of linkers and E3 ligands

  • Modular platform: More efficient synthesis of bifunctional molecules
  • Customized synthesis : From mg scale to 200+ kg scale
  • In-stock molecules: More than 350 in-stock linkers and E3 ligase ligands
E3 ligase, ligands, linkers, TPD, protein degradation
E3 ligase ligands

Leading Analytical Capabilities

  • More than 200 methods of prep-HPLC and chiral-SFC
  • Diversified techniques (RP-HPLC; NP-HPLC; SFC)
  • Various columns and modifiers available
  • Innovative online dilution system designed for PROTACs
  • Native-MS analysis for ternary complex confirmation
  • Proteomics studies to identify off-target effects

Biochemical and Biophysical assays

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

protein degrader, bifunctional, TPD, PROTAC
targeted protein degradation; complex bound to dBET23
DDB1-CRBN-BRD4(BD1) complex bound to dBET23 linker, Nature Chem. Biol. 2018, 14, 706

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 measurements
  • 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
  • Cell line-based validation assays

Binary/Ternary Complex Formation Assay Platform

  • Binary/ternary binding assays; formats on TR-FRET, AlphaScreen, Fluorescence Polarization (FP), and radioactive assays.
  • Biophysical analysis using 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 molecule design and optimization.

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