RG7388 (Idasanutlin) is the second generation inhibitor of p53-MDM2 interaction.It is orally active, potently and selectively antagonizing the p53-MDM2 interaction with Ki at low nM. Highly optimized from pyrrolidin-based derivatives, RG7388 represents a distinctive, brand-new structural category of MDM2 ligand, a significant departure from the nutlin-based, first generation ligands exemplified by RG7112. Like RG7112, RG7388 binds selectively to the p53 site on the surface of the MDM2 molecule, effectively displacing p53 from MDM2, leading to p53 stabilization and activation of the p53 pathway. However, RG7388, as compared with its predecessor, binds to the MDM2 protein with a higher potency and selectivity, and has substantially improved pharmacological properties and superior clinical efficacy at lower doses and exposures.
Synonym:RG-7388, RG7388, RO5503781
Chemical Name:4-[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carboxamido]-3-methoxybenzoic acid
Mechanism of Action:p53-MDM2 Inhibitor
Indication:Prostate cancer,Acute myeloid leukaemia, Essential thrombocythaemia; Polycythaemia vera
Developer:Roche,NHS Greater Glasgow and Clyde; University of Glasgow
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This compound and its uses are investigational and have not been approved by the US Food and Drug Administration. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. The relevance of findings in preclinical studies to humans is currently being evaluated.