您好,欢迎来到试剂信息网! [登录] [免费注册]
试剂信息网
位置:首页 > 产品库 > A-1155463
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
A-1155463
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
A-1155463图片
CAS NO:1235034-55-5
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)669.79
FormulaC35H32FN5O4S2
CAS No.1235034-55-5
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 100 mg/mL (149.3 mM)
Water: <1 mg/mL
Ethanol: 100 mg/mL (149.3 mM)
Solubility (In vivo) O=C(C1=C(CCCOC2=CC=C(C#CCN(C)C)C=C2F)SC(N3CC4=C(C=CC=C4C (NC5=NC6=CC=CC=C6S5)=O)CC3)=N1)O
Synonyms A-1155463; A 1155463; A1155463.
实验参考方法
In Vitro

In vitro activity: A-1155463 disrupts BCL-XL-BIM but not BCL-2-BIM complexes in cells. A-1155463 kills BCL-XL-dependent Molt-4 cells (EC50=70 nM) but has no measurable cytotoxicity against BCL-2-dependent RS4;11 cells (EC50>5 mM). A-1155463 induces the hallmarks of apoptosis, as evidenced by the release of cytochrome c from mitochondria, caspase activation, and the accumulation of caspase-dependent sub-G0-G1 DNA content in BCL-XL-dependent H146 cells.


Kinase Assay: A-1155463 is a highly potent and selective BCL-XL inhibitor, A-1155463 shows picomolar binding affinity to BCL-XL (Ki <0.01 nM), and>1000-fold weaker binding to BCL-2 (Ki = 80 nM) and related proteins BCL-W (Ki = 19 nM) and MCL-1 (Ki> 440 nM).


Cell Assay: Cells are treated with increasing concentration of A-1155463. Cells are assayed for viability after 72 h using the CellTiter-Glo luminescent cell viability assay according to the manufacturer’s protocol. Results are normalized to cells without treatment. EC50 is calculated using the GraphPad Prism software.

In VivoA-1155463 causes a mechanism-based and reversible thrombocytopenia in mice and inhibits H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses. he ability of A-1155463 to exert in vivo on-target activity was demonstrated through a rapid and reversible reduction in platelets in SCID-Beige mice following a single IP dose. Additionally, administration of A-1155463 to tumor bearing SCID-Beige mice afforded modest but statistically significant tumor growth inhibition. Detailed mechanistic studies of A-1155463 and combination activity with relevant chemotherapy across multiple tumor types will be reported in an accompanying manuscript. Following a single 5 mg/kg IP dose of A-1155463 in nontumor bearing SCID-Beige mice, platelet counts fall dramatically as measured at 6 h postdose and then rebound to normal levels within 72 h. Daily Dosing at 5 mg/kg IP to SCID-Beige mice that had been inoculated with BCL-XL-dependent H146 tumor cells for 14 days causes a statistically significant inhibition of tumor growth (maximum tumor growth inhibition = 44%), which is alleviated upon cessation of dosing.
Animal modelSCID-Beige Mice
Formulation & DosageFormulated in 5% DMSO, 10% EtOH, 20% Cremaphor ELP, and 65% D5W; 5 mg/kg; i.p.
References

ACS Med Chem Lett. 2014 Aug 26;5(10):1088-93; Sci Transl Med. 2015 Mar 18;7(279):279ra40; Molecular Cancer. 2015, 14(1):1-9.