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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. ABT-737 is a potent, cell-permeable mimetic of BH3 domains that avidly binds Bcl-2, Bcl-xL, and Bcl-W (Ki death proteins, leading to apoptosis. ABT-737, alone, can induce regression of some tumors in some xenograft mouse models of cancer. It shows synergy with diverse therapeutics and radiation to trigger apoptosis in cancer cells and xenografts.