RG7388

• CAT Number: I000906
• CAS Number: 1229705-06-9
• Molecular Formula: C₃₁H₂₉Cl₂F₂N₃O₄
• Molecular Weight: 616.5
• Purity: ≥95%
• Target: p53
• Solubility: DMSO: ≥ 45 mg/mL
• Storage: Store at -20°C
• IC50: 30 nM (Average IC50 of three wt-p53 cancer cell lines SJSA1, RKO, HCT116) [1]
• InChI: InChI=1S/C31H29Cl2F2N3O4/c1-30(2,3)14-24-31(15-36,19-10-9-17(32)13-21(19)34)25(18-6-5-7-20(33)26(18)35)27(38-24)28(39)37-22-11-8-16(29(40)41)12-23(22)42-4/h5-13,24-25,27,38H,14H2,1-4H3,(H,37,39)(H,40,41)/t24-,25-,27+,31-/m0/s1
• InChIKey: TVTXCJFHQKSQQM-LJQIRTBHSA-N
• SMILES: CC(C)(C)CC1C(C(C(N1)C(=O)NC2=C(C=C(C=C2)C(=O)O)OC)C3=C(C(=CC=C3)Cl)F)(C#N)C4=C(C=C(C=C4)Cl)F

RG7388 (CAT: I000906) is a small-molecule inhibitor that targets the mouse double minute 2 (MDM2) protein. MDM2 is an important negative regulator of the tumor suppressor protein p53. By binding to p53, MDM2 promotes its degradation and inhibits its transcriptional activity. RG7388 disrupts the MDM2-p53 interaction, leading to the stabilization and activation of p53. This activation of p53 can induce cell cycle arrest, and apoptosis, and inhibit tumor growth. RG7388 has shown promise as a potential anticancer agent, particularly in tumors with wild-type p53 and overexpression of MDM2. It represents a novel therapeutic strategy for reactivating p53 function and treating various types of cancer.

Reference

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.