CAS No. : 1229705-06-9

Product Details
For research use only. Not Intended for Therapeutic Use!
Cat No:I000906
Synonyms:4-[[(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-(2,2-dimethylpropyl)pyrrolidine-2-carbonyl]amino]-3-methoxybenzoic acid
Molecular Formula:C₃₁H₂₉Cl₂F₂N₃O₄
Molecular Weight:616.5
IC50:30 nM (Average IC50 of three wt-p53 cancer cell lines SJSA1, RKO, HCT116) [1]
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Appearance:Solid powder
Purity: > 98%
Cat No:I000906
Cas No:1229705-06-9

RG7388(cas 1229705-06-9) is an oral, selective, small molecule MDM2 antagonist that inhibits binding of MDM2 to p53.
RG7388 binds to MDM2 blocking the interaction between the MDM2 protein and the transcriptional activation domain of the tumor suppressor protein p53. By preventing the MDM2-p53 interaction, p53 is not enzymatically degraded and the transcriptional activity of p53 is restored. This may lead to p53-mediated induction of tumor cell apoptosis. 

1 J Med Chem. 2013 Jul 25;56(14):5979-83. doi: 10.1021/jm400487c. Epub 2013 Jul 16.
Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development.
Ding Q(1), Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B.
Author information:
(1)Discovery Chemistry, ‡Discovery Technologies, §Discovery Oncology, ∥Non-Clinical Development, Roche Research Center, Hoffmann-La Roche, Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.

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. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity.
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