Apoptosis Activator 2 is a potent apoptosis activator; increases procaspase-9 processing and subsequent caspase-3 activation. IC50 value: 4-9 uM(Leukemia origin cells)[1] Target: Apoptosis activator in vitro: Apoptosis Activator 2 promotes the cytochrome c-dependent oligomerization of Apaf-1 into the mature apoptosome. Apoptosis Activator 2 exerted a cytostatic effect on the majority of cell lines tested, inhibiting cell growth by 50–100% at 10 μM in 40 of 48 cell lines tested. Apoptosis Activator 2 exerted a cytotoxic effect, reducing the cell numbers by 10–50% and 50–100% in four and eight cell lines, respectively, from the initial levels when tested at 10 μM. At 100 μM Apoptosis Activator 2 exhibited 100% cytotoxicity in virtually all cell lines, an effect that may be due to nonspecific toxicity. Of the cancer cell lines tested in the panel, cell lines of lymphoid origin (CCRF-CEM, MOLT-4, and Jurkat) were quite sensitive to compound 2-induced killing, with IC50 values ranging from 4 to 9 μM [1]. Apoptosis Activator 2 is a potent and selective carboxylesterase inhibitor with Ki of 67/31/65 nM for hiCE/hCE/rCE respectively, also has less inhibition on AChE/BChE with Ki of 48.2/12.6 uM [2].

• [1]. Nguyen JT, et al. Direct activation of the apoptosis machinery as a mechanism to target cancer cells. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7533-8.

  [2]. Hyatt JL, et al. Selective inhibition of carboxylesterases by isatins, indole-2,3-diones. J Med Chem. 2007 Apr 19;50(8):1876-85.