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Targeted Protein degradation is emerging as a transformative new therapeutic modality. Given the immense scope of the mechanism and its inherent difficulties, it is important to have the right set of people dedicated to this field. We at Syngene have considerable experience in the field of PROTACs, with expertise in solving the synthetic chemistry and purification challenges. Our world-class targeted protein degradation team of 200+ scientists have worked on advancing PROTACs programs for several clients and are adept at running the primary screening assays and DMPK studies for this class of molecules. Syngene also has strong expertise in the synthesis of PROTACs, starting from PROTAC libraries and extending all the way to multigram synthesis of PROTACs for PK/PD studies. We have successfully synthesized multigram quantities of partial PROTACs consisting of various linkers such as alcohols, halides, acids and amines attached to ligands for E3 ligases. We also have strong capabilities in the synthesis of novel CRBN, VHL, IAP and MDM2 ligands for PROTACs. We have helped our partners in identifying multiple lead optimized compounds through optimization of different components of PROTACs.

Our PROTACs capabilities

  • Single compound mode optimization
  • Targeted library synthesis – 90+ libraries completed with >99 % success rate (LCMS purity > 90% with each library consisting of 24 compounds)
  • PROTAC degrader Optimization – CRBN ligands, VHL ligands, IAP and MDM2 ligands
  • Synthesis and modifications of E3 ligase ligands
  • Primary screening assays SAR development – PROTAC: E3: Ligand engagement assays (cell free), PROTAC: E3: Ligand degradation assays (Cell based)
  • PROTAC based screening platforms – Protein dimerization assays, binding FP assays, HiBit assays, ADP-Glo assays, solubility assays, viability assays, phospho assays
  • In Vitro ADME assays – PPB, intrinsic permeability, CYP Inhibition, MetIDs, target toxicity, bidirectional Caco-2 permeability/LLC-PK1-MDR1
  • PK studies – High quality rodent cassette studies, single dose oral and IV PK studies, tissue exposure studies, blood and plasma PK studies

PROTAC – based screening platforms at Syngene

Brochure - Targeted Protein Degradation PROTACs
Case Study - Harnessing Targeted Protein Degradation
Blog - Development of degraders: A Medicinal Chemistry perspective
Play Video
Webinar – Targeted Protein Degradation: A novel therapeutic modality
Play Video
Science Exchange Syngene Interview with Kenneth Barr Head of Discovery Services
Play Video
Reinventing ADME PK Profiling Strategy for PROTACs discovery

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