Figure 3.

Structural view of BH3 mimetics. Obatoclax (GX15-070) is a Bcl-2 homology domain-3 (BH3) mimetic. It occupies a hydrophobic cleft within the BH3-binding groove of Bcl-2, antagonizing Bcl-2 and thus inducing apoptosis. Gossypol is a natural phenol derived from the cotton plant (genus: Gossypium). The phenolic aldehyde permeates cells and acts as an inhibitor for several dehydrogenase enzymes and in particular in its (R)-configuration (known as AT-101) it acts as a pan-Bcl-2-family inhibitor, capable to bind and inhibit most antiapoptotic Bcl-2-family members. Abt-737 is a small-molecule BH3 mimetic developed by Abbott that binds to the hydrophobic BH3-binding groove of antiapoptotic Bcl-2-family members. ABT-737 binds with high affinity (Ki ≤1  nM) to Bcl-xl, Bcl-2 and Bcl-w, but not to the less-homologous proteins Bcl-b, Mcl-1 and A1. Abt-263 (Navitoclax, Abbott Laboratories) is structurally related to Abt-737. It represents an orallybioavailable small-molecule Bad-like BH3 mimetic which efficiently antagonizes antiapoptotic Bcl-2-family members (Ki's of <1 nM for Bcl-2, Bcl-xl and Bcl-w). Abt-199, generated by Abbott is a high-affinity Bcl-2-selective small-molecule BH3 mimetic. It is not interacting with Bcl-xl and thus not interfering with platelet homeostasis