RG-7112

RG-7112 is an inhibitor of mouse double-minute 2 protein (MDM2, IC50 = 0.018 µM), an E3 ubiquitin ligase that ubiquitinates the tumor suppressor p53 and also acts as a negative regulator of p53 transcriptional activity. RG-7112 binds to the p53 binding pocket of MDM2. It increases the levels of p53 and its transcriptional targets in SJSA-1 osteosarcoma cells. It inhibits proliferation in cancer cell lines expressing wild-type p53 (IC50s = 0.18-2.2 µM) and cell lines expressing mutant p53 (IC50s = 5.7-20.3 µM). RG-7112 also prevents and reduces tumor growth in an SJSA-1 mouse xenograft model when administered at doses of 50 and 100 mg/kg per day, respectively. However, it inhibits thrombopoiesis in vivo, decreasing platelet counts in rats when administered at doses of 50 and 100 mg/kg and in cynomolgus monkeys at doses of 10 and 20 mg/kg.Formal Name: [(4S,5R)-4,5-bis(4-chlorophenyl)-2-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydro-4,5-dimethyl-1H-imidazol-1-yl][4-[3-(methylsulfonyl)propyl]-1-piperazinyl]-methanone. CAS Number: 939981-39-2. Synonyms: RO5045337. Molecular Formula: C38H48Cl2N4O4S. Formula Weight: 727.8. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: :, DMF: 25 mg/ml, DMSO: 12.5 mg/ml, Ethanol: 20 mg/ml. lambdamax: 214, 251 nm. SMILES: CS(CCCN1CCN(C(N2C(C3=CC=C(C(C)(C)C)C=C3OCC)=N[C@](C4=CC=C(Cl)C=C4)(C)[C@@]2(C)C5=CC=C(Cl)C=C5)=O)CC1)(=O)=O. InChi Code: InChI=1S/C38H48Cl2N4O4S/c1-8-48-33-26-29(36(2,3)4)14-19-32(33)34-41-37(5,27-10-15-30(39)16-11-27)38(6,28-12-17-31(40)18-13-28)44(34)35(45)43-23-21-42(22-24-43)20-9-25-49(7,46)47/h10-19,26H,8-9,20-25H2,1-7H3/t37-,38+/m0/s1. InChi Key: QBGKPEROWUKSBK-QPPIDDCLSA-N.