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, and Screening: Click HERE to view our brochure

  • 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
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

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
  • Protein analysis to identify off-target effects

Biochemical and Biophysical assays

WuXi AppTec’s integrated biology and chemistry 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

Target validation

  • Target validation (dTAG, SMASh tag, Halo tag)
  • Target deconvolution

Biochemical/biophysical assay

  • POI-PROTAC or E3-PROTAC binary binding assay (TR-FRET, FP, SPR, MST/TRIC/SPS)
  • POI-PROTAC-E3 ternary complex formation assay (TR-FRET, AlphaScreen, SPR, MST/TRIC/SPS)
  • POI ubiquitination assay (TR-FRET, AlphaScreen)

Cellular assay

  • POI or E3 engagement assay (NanoBRET)
  • POI-PROTAC-E3 ternary complex formation assay (NanoBiT, NanoBRET)
  • POI ubiquitination assay (pull-down/WB, NanoBRET)
  • POI degradation assay (HiBiT, In-cell Western, ELISA, AlphaLISA, TR-FRET, WB/JESS)
  • POI functional assay, neo-substrate degradation profiling, global proteomics

Hit  Finding

  • Ready-to-screen libraries with diverse warheads and linkers
  • One stop screening for both POI and linker with bifunctional DEL
  • Ternary complex screening with On-Bead DEL

in vivo pharmacology and PK/PD analysis, in vitro ADME/Tox

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