ABT-737
(Synonyms: ABT 737, ABT737) 目录号 : GC17234
ABT-737作为一种BH3模拟药物，是Bcl-2家族的抑制剂，可抑制Bcl 2、Bcl-xL和Bcl-w的活性，IC50值<1nM。
Cas No.:852808-04-9
Sample solution is provided at 25 µL, 10mM.
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ABT-737, as a BH3 analog, is an inhibitor of the Bcl-2 family that suppresses the activity of Bcl-2, Bcl-xL, and Bcl-w[1], with an IC50 value <1nM[2].Bcl-2 and Bcl-xL are two key anti-apoptotic proteins within the Bcl-2 family. They localize to mitochondria and regulate mitochondrial outer membrane permeability. These proteins inhibit apoptosis, and their overexpression is closely associated with the onset and progression of various diseases[3]. ABT 737 competitively binds to the BH3 domain, specifically inhibiting the interaction between Bcl-2/Bcl-xL and Bak/Bax, thereby inducing apoptosis through the mitochondrial pathway[4].
In vitro, treatment of cisplatin-resistant ovarian cancer cells A2780/DDP with ABT-737 (0-80μM) for 24-48 hours resulted in a time- and dose-dependent decrease in cell survival rate, while significantly enhancing cisplatin-induced activation levels of JNK and ASK1[4]. Treatment of human UC cells (UMUC3 and 5637) with ABT-737 (0–40μM) for 12 hours significantly inhibited cell survival in a dose-dependent manner[5]. Co-treatment of DLD1 cells with an immunotoxin targeting human transferrin receptor (1ng/mL) and ABT-737 (10μM) for 48 hours resulted in caspase-3 activation, indicating cell death via the apoptotic pathway [6].
In vivo, intra-tracheal administration of 50μL carrier solution containing 100μg ABT-737 significantly alleviated AHR symptoms in mice with airway inflammation models and promoted eosinophil apoptosis[7].In vivo, treatment with ABT-737 (100mg/kg) via intraperitoneal injection for 21 days in patient-derived xenograft (PDX) mouse models of small cell lung cancer (SCLC) resulted in minor tumor shrinkage during the treatment period. Combination therapy with ABT-737 and rapamycin (20mg/kg) produced sustained antitumor activity, leading to tumor regression, with efficacy persisting beyond the treatment period [8].
References:
[1] Ou YC, Li JR, Wang JD, et al. Liao SL, Lu HC and Chen CJ: Aspirin restores ABT 737 mediated apoptosis in human renal carcinoma cells. Biochem Biophys Res Commun 502: 187 193, 2018.
[2] Oltersdorf, T., et al. (2005). An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature, 435(7042), 677-681.
[3] Li X, Guo Y, Xing Z, et al. ABT 737 increases cisplatin sensitivity through the ROS ASK1 JNK MAPK signaling axis in human ovarian cancer cisplatin resistant A2780/DDP cells[J]. Oncol Rep. 2024 Sep;52(3):122.
[4] Whitecross KF, Alsop AE, Cluse LA, et al.Lindemann RK and Johnstone RW: Defining the target specificity of ABT 737 and synergistic antitumor activities in combination with histone deacetylase inhibitors. Blood 113: 1982 1991, 2009.
[5] Cheng R, Liu X, Wang Z,et al. a Bcl 2 family inhibitor, has a synergistic effect with apoptosis by inducing urothelial carcinoma cell necroptosis. Mol Med Rep. 2021 Jun;23(6):412.
[6] Fitzgerald DJ, Moskatel E, Ben-Josef G,et al.Enhancing immunotoxin cell-killing activity via combination therapy with ABT-737. Leuk Lymphoma. 2011 Jun;52 Suppl 2(Suppl 2):79-81. doi: 10.3109/10428194.2011.569961.
[7] Tian BP, Xia LX, Bao ZQ, et al. Bcl-2 inhibitors reduce steroid-insensitive airway inflammation. J Allergy Clin Immunol. 2017 Aug;140(2):418-430. doi: 10.1016/j.jaci.2016.11.027. Epub 2016 Dec 31. Erratum in: J Allergy Clin Immunol. 2021 Jul;148(1):281.
[8] Gardner EE, Connis N, Poirier JT,et al.Rapamycin rescues ABT-737 efficacy in small cell lung cancer. Cancer Res. 2014 May 15;74(10):2846-56. doi: 10.1158/0008-5472.CAN-13-3460. Epub 2014 Mar 10.
ABT-737作为一种BH3模拟药物，是Bcl-2家族的抑制剂，可抑制Bcl 2、Bcl-xL和Bcl-w的活性[1]，IC50值<1nM[2]。Bcl-2和Bcl-xL是Bcl-2家族中两个关键的抗凋亡蛋白，它们定位于线粒体并调控线粒体外膜通透性。这两种蛋白能够抑制细胞凋亡的发生，其高表达与多种疾病的发生发展密切相关[3]。ABT 737可通过竞争性结合BH3结构域，特异性抑制Bcl 2/Bcl xL与Bak/Bax的结合，进而通过线粒体凋亡途径诱导细胞凋亡[4]。
在体外，ABT-737（0-80μM）处理顺铂耐药卵巢癌细胞A2780/DDP 24-48h，细胞存活率呈时间和剂量依赖性下降，并且能显著增强顺铂诱导的JNK和ASK1活化水平[4]。ABT-737（0-40μM）处理UC细胞（UMUC3和5637） 12h，以剂量依赖性方式显著抑制了细胞存活率[5]。靶向人转铁蛋白受体的免疫毒素（1ng/mL）与ABT-737（10μM）联合使用处理DLD1细胞48小时时，可观察到caspase 3的激活，表明通过凋亡途径引发了细胞死亡[6]。
在体内，经气管内给药途径给予50μL含100μg ABT-737的载体溶液可显著减轻气道炎症模型小鼠的AHR症状，促进嗜酸性粒细胞凋亡[7]。在体内，ABT-737（100mg/kg）通过腹腔注射治疗SCLC PDX模型小鼠21天，持续治疗期间肿瘤出现微小缩小，ABT-737和雷帕霉素（20mg/kg）联合治疗可产生持续抗肿瘤活性，导致肿瘤消退，并且疗效在治疗期结束后仍持续存在[8]。
| Cell experiment [1]: | |
Cell lines | UC cells |
Preparation Method | UC cells were seeded in 96-well plates at 10,000 cells per well and incubated for 24h at 37˚C in 5%CO2. They were treated with ABT-737 at 0, 2.5, 5, 10, 20 and 40µM for 12h.MTT (20µl) was added to each well and incubated for 4h at 37˚C in 5% CO2 . Then, 150µl DMSO was added to each well to dissolve the formazan crystals. Finally, the absorbance was measured at 570nm using an automated microplate reader. |
Reaction Conditions | 0, 2.5, 5, 10, 20, 40μM; 12h |
Applications | ABT 737 significantly inhibits UC cell proliferation in a concentration-dependent manner. |
| Animal experiment [2]: | |
Animal models | SCLC PDX Model Mice |
Preparation Method | UC cells were subcutaneously injected into female C.B.-17 severe combined immunodeficiency (scid) mice aged 4 to 6 weeks at the time of PDX injection/transplantation. When tumor volume reached 150mm³, mice were randomly assigned to treatment groups (5–6 mice per group) and received daily intraperitoneal injections of solvent, ABT-737 (100mg/kg), rapamycin (20mg/kg), etoposide (12mg/kg on days 1, 4, and 9), or combination therapy for 21 days. Tumor volume was measured every 3 days. |
Dosage form | 100mg/kg/day for 21days; i.p. |
Applications | When used alone, ABT-737 induced minimal tumor shrinkage during continuous treatment. Combination therapy with ABT-737 and rapamycin produced sustained antitumor activity, leading to tumor regression in SCLC PDX model mice. The therapeutic effect persisted even after the treatment period concluded. |
References: | |
| Cas No. | 852808-04-9 | SDF | |
| 别名 | ABT 737, ABT737 | ||
| 化学名 | 4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylbenzamide | ||
| Canonical SMILES | CN(C)CCC(CSC1=CC=CC=C1)NC2=C(C=C(C=C2)S(=O)(=O)NC(=O)C3=CC=C(C=C3)N4CCN(CC4)CC5=CC=CC=C5C6=CC=C(C=C6)Cl)[N+](=O)[O-] | ||
| 分子式 | C42H45ClN6O5S2 | 分子量 | 813.43 |
| 溶解度 | ≥ 40.67mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
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