RG7388 (Idasanutlin)

Description: RG7388 (also known as Idasanutlin and RO5503781) is a novel, potent and highly selective antagonist of the p53-MDM2 protein-protein interaction with IC50 of 6 nM. Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7388 exerts its effect by binding to MDM2 and blocking the interaction between MDM2 protein and the tumor suppressor protein p53. By disrupting the MDM2-p53 interaction, p53 is not degraded enzymatically and the transcriptional activity of p53 is restored, which results in the p53-mediated induction of tumor cell apoptosis. MDM2 is a negative regulator of the p53 pathway and is often overexpressed in tumor cells. Therefore, RG7388 has potential anticancer activity as a MDM2 antagonist.

References: J Med Chem. 2013 Jul 25; 56(14):5979-83; Clin Cancer Res. 2014 Jul 15; 20(14):3742-52.

Idasanutlin; RG-7388; RG 7388; RG7388; RO5503781; RO-5503781; RO 5503781

Chemical Name: 4-((2R, 3S, 4R, 5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid.