WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205764
CAS#: 873652-48-3 (free base)
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.
MedKoo Cat#: 205764
Name: GDC-0152 free base
CAS#: 873652-48-3 (free base)
Chemical Formula: C25H34N6O3S
Exact Mass: 498.24131
Molecular Weight: 498.646
Elemental 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
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | GDC-0152 is a potent IAPs inhibitor, and binds to the BIR3 domains of XIAP, cIAP1, cIAP2 and the BIR domain of ML-IAP with Ki values of 28 nM, 17 nM, 43 nM and 14 nM, respectively. |
| In vitro activity: | IAP inhibitor GDC-0152 treatment for 3 or 4 h significantly increased granulocyte cell death at the 100 μM dose only (One-way ANOVA, Tukey HSD, p < 0.02), indicating potential cytotoxicity at this concentration. Reference: Dev Comp Immunol. 2022 Apr;129:104339. https://pubmed.ncbi.nlm.nih.gov/34998862/ |
| In vivo activity: | Bioluminescence readings during the first 5 weeks after implantation demonstrated that GDC-0152 strongly suppressed tumor growth (Fig. 1a). Tumors regrew after GDC-0152 treatment ceased, as reflected by the weights of the tumors and the bioluminescence reading taken a week after the last drug administration. Confirming the anti-osteosarcoma activity of GDC-0152 detected using bioluminescence and via tumor weights at endpoint (Fig. 1a), tumors in GDC-0152-treated mice were less metabolically active and significantly smaller than the untreated tumors (Fig. 1b-e). Reference: BMC Cancer. 2019 Sep 14;19(1):924. https://pubmed.ncbi.nlm.nih.gov/31521127/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 25.0 | 50.14 | |
| DMF:PBS (pH 7.2) (1:1) | 0.5 | 1.0 | |
| DMSO | 69.67 | 139.71 | |
| Ethanol | 53.0 | 106.29 |
The following data is based on the product molecular weight 498.646 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Witkop EM, Wikfors GH, Proestou DA, Lundgren KM, Sullivan M, Gomez-Chiarri M. Perkinsus marinus suppresses in vitro eastern oyster apoptosis via IAP-dependent and caspase-independent pathways involving TNFR, NF-kB, and oxidative pathway crosstalk. Dev Comp Immunol. 2022 Apr;129:104339. doi: 10.1016/j.dci.2022.104339. Epub 2022 Jan 5. PMID: 34998862. 2. Soubéran A, Cappaï J, Chocry M, Nuccio C, Raujol J, Colin C, Lafitte D, Kovacic H, Quillien V, Baeza-Kallee N, Rougon G, Figarella-Branger D, Tchoghandjian A. Inhibitor of Apoptosis Proteins Determines Glioblastoma Stem-Like Cell Fate in an Oxygen-Dependent Manner. Stem Cells. 2019 Jun;37(6):731-742. doi: 10.1002/stem.2997. Epub 2019 Mar 28. PMID: 30920104. 3. Shekhar TM, Burvenich IJG, Harris MA, Rigopoulos A, Zanker D, Spurling A, Parker BS, Walkley CR, Scott AM, Hawkins CJ. Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice. BMC Cancer. 2019 Sep 14;19(1):924. doi: 10.1186/s12885-019-6103-5. PMID: 31521127; PMCID: PMC6744692. 4. 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. Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical 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. PMID: 22413863; PMCID: PMC3366583. |
| In vitro protocol: | 1. Witkop EM, Wikfors GH, Proestou DA, Lundgren KM, Sullivan M, Gomez-Chiarri M. Perkinsus marinus suppresses in vitro eastern oyster apoptosis via IAP-dependent and caspase-independent pathways involving TNFR, NF-kB, and oxidative pathway crosstalk. Dev Comp Immunol. 2022 Apr;129:104339. doi: 10.1016/j.dci.2022.104339. Epub 2022 Jan 5. PMID: 34998862. 2. Soubéran A, Cappaï J, Chocry M, Nuccio C, Raujol J, Colin C, Lafitte D, Kovacic H, Quillien V, Baeza-Kallee N, Rougon G, Figarella-Branger D, Tchoghandjian A. Inhibitor of Apoptosis Proteins Determines Glioblastoma Stem-Like Cell Fate in an Oxygen-Dependent Manner. Stem Cells. 2019 Jun;37(6):731-742. doi: 10.1002/stem.2997. Epub 2019 Mar 28. PMID: 30920104. |
| In vivo protocol: | 1. Shekhar TM, Burvenich IJG, Harris MA, Rigopoulos A, Zanker D, Spurling A, Parker BS, Walkley CR, Scott AM, Hawkins CJ. Smac mimetics LCL161 and GDC-0152 inhibit osteosarcoma growth and metastasis in mice. BMC Cancer. 2019 Sep 14;19(1):924. doi: 10.1186/s12885-019-6103-5. PMID: 31521127; PMCID: PMC6744692. 2. 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. Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical 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. PMID: 22413863; PMCID: PMC3366583. |
1: 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. Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical 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.
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).
