RO8994

• CAT Number: I001185
• CAS Number: 1309684-94-3
• Molecular Formula: C₃₁H₃₁Cl₂FN₄O₄
• Molecular Weight: 613.51
• Purity: ≥95%
• Synonyms: RO8994; CHEMBL3109036; 1309684-94-3; SCHEMBL221002
• Target: Metabolic Enzyme/Protease
• Solubility: DMSO: ≥ 45 mg/mL
• Storage: 3 years -20C powder
• IC50: 5 nM (in HTRF binding assays), 20 nM (in MTT proliferation assays)
• IUPAC Name: (2'R,3R,3'S,5'S)-N-(4-carbamoyl-2-methoxyphenyl)-6-chloro-3'-(3-chloro-2-fluorophenyl)-5'-(2,2-dimethylpropyl)-2-oxospiro[1H-indole-3,4'-pyrrolidine]-2'-carboxamide
• InChI: InChI=1S/C31H31Cl2FN4O4/c1-30(2,3)14-23-31(18-10-9-16(32)13-21(18)37-29(31)41)24(17-6-5-7-19(33)25(17)34)26(38-23)28(40)36-20-11-8-15(27(35)39)12-22(20)42-4/h5-13,23-24,26,38H,14H2,1-4H3,(H2,35,39)(H,36,40)(H,37,41)/t23-,24-,26+,31+/m0/s1
• InChIKey: MURAVORBGFDSMA-ISKXDESKSA-N
• SMILES: CC(C)(C)CC1C2(C(C(N1)C(=O)NC3=C(C=C(C=C3)C(=O)N)OC)C4=C(C(=CC=C4)Cl)F)C5=C(C=C(C=C5)Cl)NC2=O

RO8994 (Cat.No:I001185) is a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitor, with IC50 of 5 nM (HTRF binding assays) and 20 nM (MTT proliferation assays).

Reference

1:Bioorg Med Chem. 2014 Aug 1;22(15):4001-9. doi: 10.1016/j.bmc.2014.05.072. Epub 2014 Jun 11. Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy.Zhang Z,Ding Q,Liu JJ,Zhang J,Jiang N,Chu XJ,Bartkovitz D,Luk KC,Janson C,Tovar C,Filipovic ZM,Higgins B,Glenn K,Packman K,Vassilev LT,Graves B, PMID: 24997575 DOI: 10.1016/j.bmc.2014.05.072
Abstract: The field of small-molecule inhibitors of protein-protein interactions is rapidly advancing and the specific area of inhibitors of the p53/MDM2 interaction is a prime example. Several groups have published on this topic and multiple compounds are in various stages of clinical development. Building on the strength of the discovery of RG7112, a Nutlin imidazoline-based compound, and RG7388, a pyrrolidine-based compound, we have developed additional scaffolds that provide opportunities for future development. Here, we report the discovery and optimization of a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitors, culminating in RO8994. Copyright © 2014 Elsevier Ltd. All rights reserved.