生物活性

• 靶点

  Bcl-2 EC50:30.3nM

  Bcl-w EC50:197.8nM

  Bcl-xL EC50:78.7nM

• 描述The B-cell lymphoma 2 (Bcl-2) family of proteins is composed of both antiapoptotic members, such as Bcl-2, Bcl-xL as well as Bcl-w, and proapoptotic members. Up-regulation of the pro-survival Bcl-2 family proteins is one of the primary means for cancer cells to evade apoptosis. ABT-737 is a selective inhibitor of Bcl-2 family with EC50 values of 78.7nM, 30.3nM and 198.8nM for BCL-XL, BCL-2 and BCL-W (measured by FP assay), respectively, with almost no inhibition on BCL-B, BFL-1 and MCL-1. ABT-737 can inhibit cell growth with IC50 values of 50nM, 80nM, 80nM, 2μM and 5μM for leukemic cells HL60, KG1, NB4, U937 and OCI-AML3 cells, as well as and induce apoptosis at dose of 100nM for 12 or 24h in HL60. As a BH3 mimetic small-molecule, the in vitro studies showed that ABT-737 disrupted BCL-2/BAX heterodimerization and improved the apoptosis throuth inducing BAX change to a “prodeath'' conformation in AML cells. Both inhibition of BCL-2 phosphorylation and suppression of MCL-1 expression could enhance ABT-737-mediated apoptosis. Intraperitoneal administration of ABT-737 at dose of 20 and 30mg/kg suppressed the leukemia burden by 48% and 53%, respectively, as well as significantly extended survival of leukemia model. A similar inhibition of leukemia burden was also observed in a human xenograft leukemia model with KG-1 cells^[1].
• 作用机制ABT-737 is a BH3 mimetic small-molecule that can occupies the BH3 binding groove of BCL-2.^[1]

• 动物研究
  剂量	Mice: min = 25 mg/kg[2], max = 100 mg/kg[3]
  给药途径	i.p., i.v.