Strategies to Reduce the On-Target Platelet Toxicity of Bcl-x_L Inhibitors: PROTACs, SNIPERs and Prodrug-Based Approaches.

ABSTRACT: Apoptosis is a highly regulated cellular process. Aberration in apoptosis is a common characteristic of various disorders. Therefore, proteins involved in apoptosis are prime targets in multiple therapies. Bcl-x_L is an antiapoptotic protein. Compared to other antiapoptotic proteins, the expression of Bcl-x_L is common in solid tumors and, to an extent, in some leukemias and lymphomas. The overexpression of Bcl-x_L is also linked to survival and chemoresistance in cancer and senescent cells. Therefore, Bcl-x_L is a promising anticancer and senolytic target. Various nanomolar range Bcl-x_L inhibitors have been developed. ABT-263 was successfully identified as a Bcl-x_L /Bcl-2 dual inhibitor. But it failed in the clinical trial (pha

SUBMITTER: Negi A 

PROVIDER: S-EPMC9311450 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature