Current overview on the clinical update of Bcl-2 anti-apoptotic inhibitors for cancer therapy.

Current overview on the clinical update of Bcl-2 anti-apoptotic inhibitors for cancer therapy. Eur J Pharmacol. 2019 Sep 05;:172655 Authors: Suvarna V, Singh V, Murahari M Abstract Apoptosis is one of the major mechanisms exhibited in response to cell death and induction of apoptosis in tumour cells signifies a potential target for cancer therapy. Bcl-2 family proteins play a key role in regulation of the apoptotic pathway. Bcl-2 overexpression is commonly associated with various cancers including breast cancer, prostate cancer, B-cell lymphomas and colorectal adenocarcinomas etc. Thus, Bcl-2 is a novel anti-cancer target attracting medicinal chemists across the globe. Research investigations underlying Bcl-2 target have resulted in the generation of small molecule inhibitors, named as 'BH3-mimetics' (Bcl-2 homology 3 mimetics). These drugs display binding to pro-survival Bcl-2 proteins resulting in actuation of apoptosis of cancer cells. The first BH3 mimetics discovered as an outcome of structure-based drug design and Nuclear Magnetic Resonance (NMR)-based screening was ABT-263, an N-acylsulfonamide analogue. Thrombocytopenia a major dose-limiting toxicity, associated with ABT-263 had provoked the invention of a highly selective Bcl-2 inhibitor venetoclax. Several Bcl-2 inhibitors as small molecules are under clinical development and the results indicated that these molecules alone or in combination could be of potential applicatio...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research