GDC-0152 free base

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

Description:GDC-0152 is a second mitochondrial activator of caspases (Smac) mimetic inhibitor of IAPs (Inhibitor of Apoptosis Proteins) with potential antineoplastic activity. Smac mimetic GDC-0152 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, which may inhibit their activities and promote the induction of apoptosis through apoptotic signaling pathways. IAPs are overexpressed by many cancer cell types and suppress apoptosis by binding to and inhibiting active caspases-3, -7 and -9 via their baculoviral lAP repeat (BIR) domains.

Price and Availability

GDC-0152 free base, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 205764Name: GDC-0152 free baseCAS#: 873652-48-3 (free base)Chemical Formula: C25H34N6O3SExact Mass: 498.24131Molecular Weight: 498.64Elemental Analysis: C, 60.22; H, 6.87; N, 16.85; O, 9.63; S, 6.43

Related CAS #:873652-48-3 (free base)873581-21-6 (HCl)

Synonym:GDC0152; GDC0152; GDC 0152;RG 7419;RG-7419;RG7419.

IUPAC/Chemical Name:(S)-1-((S)-2-cyclohexyl-2-((S)-2-(methylamino)propanamido)acetyl)-N-(4-phenyl-1,2,3-thiadiazol-5-yl)pyrrolidine-2-carboxamide

InChi Key:WZRFLSDVFPIXOV-LRQRDZAKSA-N

InChi Code:InChI=1S/C25H34N6O3S/c1-16(26-2)22(32)27-21(18-12-7-4-8-13-18)25(34)31-15-9-14-19(31)23(33)28-24-20(29-30-35-24)17-10-5-3-6-11-17/h3,5-6,10-11,16,18-19,21,26H,4,7-9,12-15H2,1-2H3,(H,27,32)(H,28,33)/t16-,19-,21-/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=NS3

Technical Data

Additional Information

GDC-0152 binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2 with K(i) values of 28, 14, 17, and 43 nM, respectively. These compounds promote degradation of cIAP1, induce activation of caspase-3/7, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Compound 1 inhibits tumor growth when dosed orally in the MDA-MB-231 breast cancer xenograft model. Compound 1 was advanced to human clinical trials, and it exhibited linear pharmacokinetics over the dose range (0.049 to 1.48 mg/kg) tested. Mean plasma clearance in humans was 9 ± 3 mL/min/kg, and the volume of distribution was 0.6 ± 0.2 L/kg.  (source:  J Med Chem. 2012 May 10;55(9):4101-13).   

References

1: Flygare JA, Beresini M,Budha N, Chan H, Chan IT, Cheeti S, Cohen F, Deshayes  K, DoernerK, Eckhardt SG, Elliott LO, Feng B, Franklin MC, Reisner SF, Gazzard L,Halladay J, Hymowitz SG, La H, LoRusso P, Maurer B, Murray L, Plise E,Quan C, Stephan JP, Young SG, Tom J, Tsui V, Um J, Varfolomeev E, VucicD, Wagner AJ, Wallweber HJ, Wang L, Ware J, Wen Z, Wong H, Wong JM, WongM, Wong S, Yu R, Zobel K, Fairbrother WJ. Discovery of a potentsmall-molecule antagonist of inhibitor of apoptosis (IAP) proteins andclinical candidate for the treatment of cancer (GDC-0152). J Med Chem.2012 May 10;55(9):4101-13. doi: 10.1021/jm300060k. Epub 2012 Mar 28.PubMed PMID: 22413863; PubMed Central PMCID: PMC3366583.