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Chemical Structure| 923564-51-6 同义名 : ABT-263;A-855071
CAS号 : 923564-51-6
货号 : A204180
分子式 : C47H55ClF3N5O6S3
纯度 : 99%+
分子量 : 974.613
MDL号 : MFCD12756219
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 80 mg/mL(82.08 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

DMF: 100 mg/mL(102.6 mM)
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 2 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • Bcl-xL

    Bcl-xL, Ki:<=0.5 nM

  • Bcl-w

    Bcl-w, Ki:<=1 nM

  • Bcl-2

    Bcl-2, Ki:<=1 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-263, advanced based on ABT-737, is a potent and orally bioavailable Bcl-2 family inhibitor (Bcl-xL Ki≤0.5nM,Bcl-2 Ki≤1nM,Bcl-w Ki≤1nM, FPA assay; Bcl-xL Ki=0.4nM, TR-FRET assay; Mcl-1 IC50=550±40nM, A1 IC50=354±63nM,reported). It can disrupt Bcl-xL/Bcl-xS interaction, as well as activates Bax and cytochrome c (Cyto c) release. ABT-263 exhibited single-agent activity in SCLC and hematologic malignancies but not in the majority of other tumor types. Oral dosing of ABT-263 results in the regression of SCLC and ALL xenograft tumors in vivo. Also it enhances the activity of chemotherapeutic agents[1]. The clinical trials of ABT-263 on relapsed/refractory CLL, platinum-resistant, refractory ovarian cancer, etc. are undergoing[2].
作用机制 ABT-263 directly binds Bcl-2 as well as Bcl-xL and blocks their ability to bind to BIM.[3]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
5637 Growth Inhibition Assay IC50=3.61103 μM SANGER
697 Growth Inhibition Assay IC50=0.10839 μM SANGER
769-P Growth Inhibition Assay IC50=3.8951 μM SANGER
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
NCT01423539 Diffuse Large B-Cell Lymphoma Phase 2 Withdrawn(The NAVIGATE study h... 展开 >>as been terminated due to non-safety related reasons.) 收起 << February 2014 United States, California ... 展开 >> Fountain Valley, California, United States, 92708 United States, Florida Hudson, Florida, United States, 34667 United States, Georgia Lawrenceville, Georgia, United States, 30045 United States, Illinois Centralia, Illinois, United States, 62801 Harvey, Illinois, United States, 60426 United States, Indiana Terre Haute, Indiana, United States, 47802 United States, Kentucky Hazard, Kentucky, United States, 41701 Paducah, Kentucky, United States, 42003 United States, Maryland Rockville, Maryland, United States, 20850 United States, Missouri Jefferson City, Missouri, United States, 65109 United States, Montana Great Falls, Montana, United States, 59405 United States, Ohio Newark, Ohio, United States, 43055 United States, Tennessee Nashville, Tennessee, United States, 37203 收起 <<
NCT01053520 Healthy Female Subjects Phase 1 Completed - United States, Illinois ... 展开 >> Site Reference ID/Investigator# 23602 Waukegan, Illinois, United States, 60085 收起 <<
NCT01989585 BRAF V600E Mutation Present ... 展开 >> BRAF V600K Mutation Present Metastatic Melanoma Solid Neoplasm Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 收起 << Phase 1 Phase 2 Recruiting - United States, California ... 展开 >> University of California Davis Comprehensive Cancer Center Suspended Sacramento, California, United States, 95817 United States, Massachusetts Massachusetts General Hospital Cancer Center Withdrawn Boston, Massachusetts, United States, 02114 United States, Missouri Siteman Cancer Center at West County Hospital Suspended Creve Coeur, Missouri, United States, 63141 Washington University School of Medicine Suspended Saint Louis, Missouri, United States, 63110 Siteman Cancer Center-South County Suspended Saint Louis, Missouri, United States, 63129 Siteman Cancer Center at Christian Hospital Suspended Saint Louis, Missouri, United States, 63136 Siteman Cancer Center at Saint Peters Hospital Suspended Saint Peters, Missouri, United States, 63376 United States, New Jersey Rutgers Cancer Institute of New Jersey Recruiting New Brunswick, New Jersey, United States, 08903 Contact: Site Public Contact    732-235-8675       Principal Investigator: Janice M. Mehnert          United States, North Carolina Duke University Medical Center Recruiting Durham, North Carolina, United States, 27710 Contact: Site Public Contact    888-275-3853       Principal Investigator: James L. Abbruzzese          United States, Ohio Ohio State University Comprehensive Cancer Center Recruiting Columbus, Ohio, United States, 43210 Contact: Site Public Contact    800-293-5066    Jamesline@osumc.edu    Principal Investigator: Kari L. Kendra          United States, Texas M D Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Site Public Contact    877-312-3961       Principal Investigator: Michael A. Davies 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.03mL

0.21mL

0.10mL

5.13mL

1.03mL

0.51mL

10.26mL

2.05mL

1.03mL
参考文献

[1]Tse C, Shoemaker AR, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008 May 1;68(9):3421-8.

[2]Levy MA, Claxton DF, et al. Therapeutic inhibition of BCL-2 and related family members. Expert Opin Investig Drugs. 2017 Mar;26(3):293-301.

[3]Del Gaizo Moore V, Brown JR, et al. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest. 2007 Jan;117(1):112-21.

[4]Chen Q, Song S, et al. ABT-263 induces apoptosis and synergizes with chemotherapy by targeting stemness pathways in esophageal cancer. Oncotarget. 2015 Sep 22;6(28):25883-96.

[5]Ackler S, Xiao Y, et al. ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Mol Cancer Ther. 2008 Oct;7(10):3265-74.