ABT-737 是一种 BH3 模拟物,是一种有效的Bcl-2、Bcl-xL和Bcl-w抑制剂,EC50分别为 30.3 nM、78.7 nM 和 197.8 nM。ABT-737 诱导 BCL-2/BAX 复合物的破坏和 BAK 依赖性但不依赖 BIM 的内在凋亡途径激活。ABT-737 诱导自噬,并且具有用于急性髓系白血病 (AML) 研究的潜力。
生物活性 | ABT-737, a BH3 mimetic, is a potentBcl-2,Bcl-xLandBcl-winhibitor withEC50s 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 intrinsicapoptoticpathway. ABT-737 inducesautophagyand has the potential for acute myeloid leukemia (AML) research[1][2][3]. |
IC50& Target[1] | Bcl-2 30.3 nM (EC50) | Bcl-xL 78.7 nM (EC50) | Bcl-W 197.8 nM (EC50) | Bcl-B 1820 nM (EC50) | Bfl-1 >10 μM (EC50) | Mcl-1 >10 μM (EC50) |
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体外研究 (In Vitro) | ABT-737 binds BCL-2, BCL-XL, and BCL-W with high affinity (Ki<1 nm) but binds weakly (ki>460 nM) to other antiapoptotic BCL-2 family members, including MCL-1 and BFL-1. ABT-737 binds the BH3-binding groove of BCL-XLand 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 O2consumption 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 O2consumption rate in B-cell lymphoma cells[3].
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体内研究 (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].
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 50 mg/mL(61.47 mM;Need ultrasonic) 配制储备液 1 mM | 1.2294 mL | 6.1468 mL | 12.2936 mL | 5 mM | 0.2459 mL | 1.2294 mL | 2.4587 mL | 10 mM | 0.1229 mL | 0.6147 mL | 1.2294 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.5 mg/mL (3.07 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (3.07 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (3.07 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (3.07 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (3.07 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (3.07 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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