Discovery of novel benzimidazole derivatives as potent p300 bromodomain inhibitors with anti-proliferative activity in multiple cancer cells.

Basic Information

ID: ALA5120873

Journal: Bioorg Med Chem

Title: Discovery of novel benzimidazole derivatives as potent p300 bromodomain inhibitors with anti-proliferative activity in multiple cancer cells.

Authors: Chen Z, Li J, Yang H, He Y, Shi Q, Chang Q, Liu R, Huang X, Li Y.

Abstract: Adenovirus E1A-associated 300-k_D protein (p300) bromodomain, which regulates gene expression by recognizing acetylated lysine (KAc) of histone, is a promising target for the treatment of cancer. Herein, a series of potent p300 bromodomain inhibitors with novel CBP30-based scaffolds was discovered through bioisosterism and conformational restriction strategies. The most promising compound 1u showed more potent inhibitory activity (IC₅₀ = 49 nM) against p300 bromodomain and anti-proliferative activity in various cancer cell lines compared to CBP30. Moreover, 1u suppressed the expression of c-Myc and induced G₁/G₀ phase arrest and apoptosis in OPM-2 cells more potently than CBP30. This study provides new lead compounds for further research on the biological functions of p300.

CiteXplore: 35569250

DOI: 10.1016/j.bmc.2022.116784

Patent ID: ┄

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