GDC-0152

• CAT Number: I005261
• CAS Number: 873652-48-3
• Molecular Formula: C25H34N6O3S
• Molecular Weight: 498.6
• Purity: ≥95%
• Target: IAP
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 28/14/17/43 nM(Ki, XIAP/ML-IAP/cIAP1/cIAP2) [1]
• InChIKey: WZRFLSDVFPIXOV-LRQRDZAKSA-N

GDC-0152 (CAT: I005261) is a potent inhibitor of apoptosis proteins (IAPs), specifically binding to the BIR3 domains of XIAP, ML-IAP, cIAP1, and cIAP2 with Ki values ranging from 14 to 43 nM. In vitro studies demonstrate that GDC-0152 disrupts protein-protein interactions involving IAPs and pro-apoptotic molecules, leading to decreased cell viability and activation of caspases. GDC-0152 induces degradation of cIAP1 in melanoma cells and shows selectivity for cancer cells over normal cells. In vivo, GDC-0152 exhibits moderate hepatic clearance and plasma protein binding across multiple species, with pharmacokinetic parameters including a Cmax of 53.7 μM and AUC of 203.5 h-μM. These findings highlight the potential of GDC-0152 as an IAP inhibitor for targeted cancer therapy.

Reference

1:Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152. Tchoghandjian A, Soubéran A, Tabouret E, Colin C, Denicolaï E, Jiguet-Jiglaire C, El-Battari A, Villard C, Baeza-Kallee N, Figarella-Branger D.Cell Death Dis. 2016 Aug 4;7(8):e2325. doi: 10.1038/cddis.2016.214. PMID: 27490930 Free PMC Article2:GDC-0152 attenuates the malignant progression of osteosarcoma promoted by ANGPTL2 via PI3K/AKT but not p38MAPK signaling pathway. Yang L, Shu T, Liang Y, Gu W, Wang C, Song X, Fan C, Wang W.Int J Oncol. 2015 Apr;46(4):1651-8. doi: 10.3892/ijo.2015.2872. Epub 2015 Feb 4. PMID: 25651778 3:GDC-0152 induces apoptosis through down-regulation of IAPs in human leukemia cells and inhibition of PI3K/Akt signaling pathway. Hu R, Li J, Liu Z, Miao M, Yao K.Tumour Biol. 2015 Feb;36(2):577-84. doi: 10.1007/s13277-014-2648-8. Epub 2014 Oct 2. PMID: 25273171 4:Evaluation of metabolism and disposition of GDC-0152 in rats using 14C labeling strategy at two different positions: a novel formation of hippuric acid from 4-phenyl-5-amino-1,2,3-thiadiazole. Yue Q, Mulder T, Rudewicz PJ, Solon E, Budha N, Ware JA, Lyssikatos J, Hop CE, Wong H, Khojasteh SC.Drug Metab Dispos. 2013 Feb;41(2):508-17. doi: 10.1124/dmd.112.047019. Epub 2012 Dec 4. PMID: 23223496 Free Article5:Toxicity profile of small-molecule IAP antagonist GDC-0152 is linked to TNF-α pharmacology. Erickson RI, Tarrant J, Cain G, Lewin-Koh SC, Dybdal N, Wong H, Blackwood E, West K, Steigerwalt R, Mamounas M, Flygare JA, Amemiya K, Dambach D, Fairbrother WJ, Diaz D.Toxicol Sci. 2013 Jan;131(1):247-58. doi: 10.1093/toxsci/kfs265. Epub 2012 Sep 5. PMID: 22956632 6:Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0152 in human plasma using solid-phase extraction. Shin YG, Jones SA, Murakami SC, Budha N, Ware J, Wong H, Buonarati MH, Dean B, Hop CE.Biomed Chromatogr. 2013 Jan;27(1):102-10. doi: 10.1002/bmc.2754. Epub 2012 May 24. PMID: 22623056 7:Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). Flygare JA, Beresini M, Budha N, Chan H, Chan IT, Cheeti S, Cohen F, Deshayes K, Doerner K, 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, Vucic D, Wagner AJ, Wallweber HJ, Wang L, Ware J, Wen Z, Wong H, Wong JM, Wong M, Wong S, Yu R, Zobel K, Fairbrother WJ.J Med Chem. 2012 May 10;55(9):4101-13. doi: 10.1021/jm300060k. Epub 2012 Mar 28. PMID: 22413863 Free PMC Article