Mechanism of BH3 mimetics promoting cell apoptosis and its latest clinical research progress / 中国药理学与毒理学杂志

ABSTRACT

Targeting cell apoptosis is currently the most promising therapy for cancer treatment. The BH3-only protein, which is a member of Bcl-2 family, can bind to the pro-survival members of the family and neutralize their functional activities to induce apoptosis (ie, to isolate pro-apoptotic members of the Bcl-2 family). BH3 mimetics, a kind of small molecule compounds, has the ability to mimic the BH3-only protein to induce apoptosis. The prototype of BH3 mimetics is ABT-737, who can selectively targets on BCL-XL, BCL-2 and BCL-W (but not MCL-1 and A1). ABT-263, a derivative of ABT-737, has a better performance of inducing apoptosis and inhibiting the growth of tumor in clinical trials. At this stage, some presumably BH3 mimetics has entered the clinical stage, while a large part of them is still being characterized and tested. Basing on the mechanism of BH3-only protein, this review summarize a variety of BH3 mimetics which have been widely recognized, and show the latest developments of newly diagnosed BH3 mimetics in the field.