RO8994

RO8994 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). IC50 value: 5 nM (in HTRF binding assays), 20 nM (in MTT proliferation assays) Target: MDM2 in vitro: RO8994 represents a new generation of p53-MDM2 antagonists with marked improvement in pharmacological properties for potential clinical development. RO8994 induces dose-dependent up-regulation of p53 target genes and apoptosis in wild-type p53 cancer cells, consistent with its non-genotoxic mechanism of p53 activation. in vivo: RO8994 displays remarkable tumor growth inhibition in the wild-type p53, MDM2-amplified SJSA-1 osteosarcoma tumor xenograft model - exhibiting significant (>60%) tumor growth inhibition at the low dose of 1.56 mg/kg, tumor stasis at 3.125 mg/kg and regression at 6.25 mg/kg.

Product information

CAS Number: 1309684-94-3

Molecular Weight: 613.51

Formula: C31H31Cl2FN4O4

Chemical Name: (2'S, 3R, 4'S, 5'R)-N-(4-carbamoyl-2-methoxyphenyl)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2, 2-dimethylpropyl)-2-oxo-1, 2-dihydrospiro[indole-3, 3'-pyrrolidine]-5'-carboxamide

Smiles: CC(C)(C)C[C@@H]1N[C@H]([C@H](C2=CC=CC(Cl)=C2F)[C@]21C1=CC=C(Cl)C=C1NC2=O)C(=O)NC1=CC=C(C=C1OC)C(N)=O

InChiKey: MURAVORBGFDSMA-ISKXDESKSA-N

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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 45 mg/mL (73.35 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

References:

1. Zhang Z, et al. Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy. Bioorg Med Chem. 2014 Aug 1;22(15):4001-4009.

Products are for research use only. Not for human use.