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ABT-737

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Chemical Structure| 852808-04-9 同义名 : -
CAS号 : 852808-04-9
货号 : A821402
分子式 : C42H45ClN6O5S2
纯度 : 99%+
分子量 : 813.427
MDL号 : MFCD12756212
存储条件：

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(61.47 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

2%DMSO+40%PEG300+5%Tween80+53%water 2 mg/mL

生物活性
靶点

  • Bcl-xL

    Bcl-xL, EC50:78.7 nM

  • Bcl-B

    Bcl-B, EC50:1.82 μM

  • Bcl-w

    Bcl-w, EC50:197.8 nM

  • Bcl-2

    Bcl-2, EC50:30.3 nM
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]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
93-VU-147T Growth Inhibition Assay 72 h GI50=4.3 ± 3.5 μM 25139387
A549 0-20 μM Cell Viability Assay 72 h decreases the cell survival in a dose-dependent manner combined with aspirin 25388762
A549 20 μM Apoptosis Assay 48 h induces apoptosis significantly combined with aspirin 25388762
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01440504 - Completed - France ... 展开 >> Centre François Baclesse Caen, France, 14076 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.23mL

0.25mL

0.12mL

6.15mL

1.23mL

0.61mL

12.29mL

2.46mL

1.23mL
参考文献

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

[2]Whitecross KF, Alsop AE, et al. Defining the target specificity of ABT-737 and synergistic antitumor activities in combination with histone deacetylase inhibitors. Blood. 2009;113(9):1982-91.

[3]Jain HV, Richardson A, et al. Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas. PLoS One. 2014;9(1):e81582.