GDC-0917 (CUDC-427)

    WARNING: This product is for research use only, not for human or veterinary use.

Description: CUDC-427, also known as, GDC-0917, is an orally available, monovalent mimetic of second mitochondrial-derived activator of caspases (Smac/DIABLO) and inhibitor of IAPs (Inhibitor of Apoptosis Proteins) with potential antineoplastic activity. Smac mimetic CUDC-427 binds to the Smac binding groove on IAPs, including the direct caspase inhibitor X chromosome-linked IAP (XIAP) and the cellular IAPs 1 and 2. This inhibits the activities of these IAPs and promotes the induction of apoptosis through apoptotic signaling pathways.

Price and Availability

GDC-0917 is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Synonym: GDC0917; GDC-0917; GDC 0917; CUDC427; CUDC-427; CUDC 427.

IUPAC/Chemical Name: (S)-1-((S)-2-cyclohexyl-2-((S)-2-(methylamino)propanamido)acetyl)-N-(2-(oxazol-2-yl)-4-phenylthiazol-5-yl)pyrrolidine-2-carboxamide

InChi Key: HSHPBORBOJIXSQ-HARLFGEKSA-N

InChi Code: InChI=1S/C29H36N6O4S/c1-18(30-2)24(36)32-23(20-12-7-4-8-13-20)29(38)35-16-9-14-21(35)25(37)34-27-22(19-10-5-3-6-11-19)33-28(40-27)26-31-15-17-39-26/h3,5-6,10-11,15,17-18,20-21,23,30H,4,7-9,12-14,16H2,1-2H3,(H,32,36)(H,34,37)/t18-,21-,23-/m0/s1

SMILES Code: O=C([C@H]1N(C([C@H](C2CCCCC2)NC([C@@H](NC)C)=O)=O)CCC1)NC3=C(C4=CC=CC=C4)N=C(C5=NC=CO5)S3

Technical Data

Additional Information

 CUDC-427 is currently developed by Curis, Inc , who licensed from Genentech. CUDC-417 is an orally bioavailable small molecule that triggers tumor cell apoptosis by selectively antagonizing IAP proteins. CUDC-427 was designed to mimic the endogenous IAP antagonist, second mitochondria-derived activator of caspases/direct IAP-binding protein (Smac/DIABLO) that is released into the cytoplasm in response to pro-apoptotic stimuli. CUDC-427 has demonstrated single-agent and combination therapy anti-tumor activity in mouse xenograft tumor models when administered orally, and IND-enabling safety studies have shown it to be well tolerated when dosed daily by oral administration, potentially enabling sustained target inhibition.
 CUDC-427 is currently developed by
, who licensed from Genentech. CUDC-417 is an orally bioavailable small molecule that triggers tumor cell apoptosis by selectively antagonizing IAP proteins. CUDC-427 was designed to mimic the endogenous IAP antagonist, second mitochondria-derived activator of caspases/direct IAP-binding protein (Smac/DIABLO) that is released into the cytoplasm in response to pro-apoptotic stimuli. CUDC-427 has demonstrated single-agent and combination therapy anti-tumor activity in mouse xenograft tumor models when administered orally, and IND-enabling safety studies have shown it to be well tolerated when dosed daily by oral administration, potentially enabling sustained target inhibition.
   
 

References

1: Wong H, Gould SE, Budha N, Darbonne WC, Kadel EE 3rd, La H, Alicke B, Halladay JS, Erickson R, Portera C, Tolcher AW, Infante JR, Mamounas M, Flygare JA, Hop CE, Fairbrother WJ. Learning and Confirming with Preclinical Studies: Modeling and Simulation in the Discovery of GDC-0917, an IAP Antagonist. Drug Metab Dispos. 2013 41:2104-2113.  PubMed PMID: 24041744.