Setidegrasib

Setidegrasib
Clinical data
Other namesASP-3082
Identifiers
  • (2S,4R)-1-[(2S)-2-[4-[4-[[6-cyclopropyl-4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-7-(6-fluoro-5-methyl-1H-indazol-4-yl)-2-(oxan-4-yloxy)quinazolin-8-yl]oxymethyl]phenyl]triazol-1-yl]-3-methylbutanoyl]-4-hydroxy-N-[(1R)-2-hydroxy-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
PDB ligand
Chemical and physical data
FormulaC60H65FN12O7S
Molar mass1117.32 g·mol−1
3D model (JSmol)
  • CC1=C(C=C2C(=C1C3=C(C=C4C(=C3OCC5=CC=C(C=C5)C6=CN(N=N6)[C@@H](C(C)C)C(=O)N7C[C@@H](C[C@H]7C(=O)N[C@@H](CO)C8=CC=C(C=C8)C9=C(N=CS9)C)O)N=C(N=C4N1C[C@@H]3C[C@H]1CN3)OC1CCOCC1)C1CC1)C=NN2)F
  • InChI=InChI=1S/C60H65FN12O7S/c1-31(2)54(59(77)72-26-41(75)20-50(72)58(76)65-49(28-74)37-11-13-38(14-12-37)56-33(4)63-30-81-56)73-27-48(69-70-73)36-7-5-34(6-8-36)29-79-55-52(51-32(3)46(61)22-47-45(51)24-64-68-47)43(35-9-10-35)21-44-53(55)66-60(80-42-15-17-78-18-16-42)67-57(44)71-25-39-19-40(71)23-62-39/h5-8,11-14,21-22,24,27,30-31,35,39-42,49-50,54,62,74-75H,9-10,15-20,23,25-26,28-29H2,1-4H3,(H,64,68)(H,65,76)/t39-,40-,41+,49-,50-,54-/m0/s1
  • Key:XXWMEQMGQNHRAF-WFJRNIGCSA-N

Setidegrasib is an investigational new drug that is being evaluated by Astellas Pharma for the treatment of solid tumors. It is an PROTACs degrader of the KRAS protein harboring a G12D mutation.

Clinical trials

Setidegrasib in combination with either FOLFIRINOX or NALIRIFOX chemotherapy is currently in phase 3 clinical trials for the treatment of pancreatic cancer.

References

  1. 1 2 "Setidegrasib - Astellas Pharma". AdisInsight. Springer Nature Switzerland AG.
  2. ↑ Zhang YB, Fu JW, Liu Y, Wu RL, Liang YT, Zhang WH, et al. (July 2026). "Targeted protein degradation: bridging chemical biology and clinical translation". Acta Pharmacologica Sinica. doi:10.1038/s41401-026-01861-2. PMID 42414544.
  3. ↑ Yoshinari T, Nagashima T, Ishioka H, Inamura K, Nishizono Y, Tasaki M, et al. (August 2025). "Discovery of KRAS(G12D) selective degrader ASP3082". Nature Communications Chemistry. 8 (1) 254. Bibcode:2025CmChe...8..254Y. doi:10.1038/s42004-025-01662-4. PMC 12375097. PMID 40849515.
  4. ↑ Clinical trial number NCT07409272 for "A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given with either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People with Pancreatic Cancer" at ClinicalTrials.gov