The family of Bcl-2 proteins plays pivotal roles in either promoting or preventing apoptosis. Bcl-2 family members contain one or more of four characteristic Bcl-2 homology (BH) domains, which are crucial for function. For example, anti-apoptotic Bcl-2 family proteins prevent death signaling by heterodimerizing with pro-death proteins at their BH3 domains. BH3I-1 is a cell permeable inhibitor that blocks the binding of BH3 peptides to Bcl-xL, inducing apoptosis. It inhibits interactions of BH3 domain-containing proteins with Bcl-xL, Bcl-2, and Bcl-W, inducing apoptosis in Bcl-2 or Bcl-W expressing cells with Ki values of 43.4 and 124 μM, respectively. BH3I-1 enhances radiation sensitivity in non-small cell lung cancer cells.
