ABT-737

ABT-737, a BH3 mimetic, is a potent Bcl-2, Bcl-x_L and Bcl-w inhibitor with EC₅₀s of 30.3 nM, 78.7 nM, and 197.8 nM, respectively. ABT-737 induces the disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway. ABT-737 induces autophagy and has the potential for acute myeloid leukemia (AML) research^[1][2][3]. IC50 & Target: EC50: 78.7 nM (Bcl-xL), 30.3 nM (Bcl-2), 197.8 nM (Bcl-w)^[3] In Vitro: ABT-737 binds BCL-2, BCL-X_L, and BCL-W with high affinity (K_i<1 nM) but binds weakly (K_i>460 nM) to other antiapoptotic BCL-2 family members, including MCL-1 and BFL-1. ABT-737 binds the BH3-binding groove of BCL-X_L and BCL-2^[1].
ABT-737 (100 nM; 1-72 hours) induces apoptosis and synergizes with chemotherapy in HL-60 cells^[1].
ABT-737 (5, 7.5, 10 μM; 72 hours) causes approximately 80% HCT116 cell death. The BAX knockout variant is completely resistant to ABT-737^[1].
ABT-737 has no effect on cell cycle distribution. ABT-737 disrupts BCL-2/BAX heterodimerization and induces BAX conformational change in HL-60 leukemic cells^[1].
ABT-737 induces a BAX/BAK-dependent impairment of maximal O₂ consumption rate in sensitive cells. Stable BCL-2 overexpression in MCF10A cells induces an ABT-737-sensitive primed for death state. ABT-737 induces dose-dependent impairment of maximal O₂ consumption rate in B-cell lymphoma cells^[3]. In Vivo: ABT-737 (20, 30 mg/kg/day; i.p.; for 21 days) suppresses the leukemia burden by 48% and 53% at the 20 and 30 mg/kg dose levels, respectively, in four- to six-week-old CB.17 Scid mice with human leukemia KG-1 cells^[1].
ABT-737 significantly extends survival of mice in this aggressive leukemia model^[1].