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].

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].
ABT-737 (50 mg/kg; i.p.; once a day; for 5 days) is highly selective for lymphoid cells and inhibited allogeneic T- and B-cell responses after skin transplantation in mice^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

813.43

C₄₂H₄₅ClN₆O₅S₂

852808-04-9

Solid

Yellow to orange

CN(CC[C@@H](NC1=CC=C(C=C1[N+]([O-])=O)S(NC(C2=CC=C(C=C2)N3CCN(CC3)CC4=CC=CC=C4C5=CC=C(C=C5)Cl)=O)(=O)=O)CSC6=CC=CC=C6)C

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Konopleva M, et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell. 2006 Nov;10(5):375-88.  [Content Brief]

  [2]. Ahamed Saleem, et al. Effect of dual inhibition of apoptosis and autophagy in prostate cancer. Prostate. 2012 Sep 1;72(12):1374-81.  [Content Brief]

  [3]. Clerc P, et al. Polster BM.Rapid Detection of an ABT-737-Sensitive Primed for Death State in Cells Using Microplate-Based Respirometry.PLoS One. 2012;7(8):e42487. Epub 2012 Aug 3.  [Content Brief]

  [4]. Cippà PE, et al. The BH3-mimetic ABT-737 inhibits allogeneic immune responses. Transpl Int. 2011 Jul;24(7):722-32.  [Content Brief]