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A-1155463

Names

[ CAS No. ]:
1235034-55-5

[ Name ]:
A-1155463

[Synonym ]:
2-[8-(1,3-Benzothiazol-2-ylcarbamoyl)-3,4-dihydro-2(1H)-isoquinolinyl]-5-(3-{4-[3-(dimethylamino)-1-propyn-1-yl]-2-fluorophenoxy}propyl)-1,3-thiazole-4-carboxylic acid
4-Thiazolecarboxylic acid, 2-[8-[(2-benzothiazolylamino)carbonyl]-3,4-dihydro-2(1H)-isoquinolinyl]-5-[3-[4-[3-(dimethylamino)-1-propyn-1-yl]-2-fluorophenoxy]propyl]-
A1155463
A-1155463

Biological Activity

[Description]:

A-1155463 is a highly potent and selective BCL-XL inhibitor with an EC50 of 70 nM in Molt-4 cell.

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Bcl-2 Family
Research Areas >> Cancer

[Target]

Bcl-xL:0.01 nM (Ki)

Bcl-2:80 nM (Ki)


[In Vitro]

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) [2]. A-1155463 demonstrates strong growth inhibition of over half of the colorectal cell lines as defined by EC50 values ≤0.5 μM in the presence of 10 % FBS[3].

[In Vivo]

A-1155463 caused a mechanism-based and reversible thrombocytopenia in mice and inhibited H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses[2].

[Animal admin]

Mice: Following a single 5 mg/kg IP dose of A-1155463 in nontumor bearing SCID-Beige mice, platelet counts fell dramatically as measured at 6 h postdose and then rebounded to normal levels within 72 h. A-1155463 is then administered to SCID-Beige mice that had been inoculated with BCL-XL-dependent H146 tumor cells with a daily dose at 5 mg/kg IP for 14 days[2].

[References]

[1]. Leverson JD, et al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci Transl Med.?2015 Mar 18;7(279):279

[2]. Tao ZF, et al. Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity. ACS Med Chem Lett. 2014 Aug 26;5(10):1088-93.

[3]. Zhang H, et al. Genomic analysis and selective small molecule inhibition identifies BCL-X(L) as a critical survival factor in a subset of colorectal cancer. Mol Cancer. 2015 Jul 2;14:126.


[Related Small Molecules]

Venetoclax (ABT-199) | ABT-263 | S63845 | ABT-737 | Obatoclax Mesylate | A-1210477 | WEHI-539 hydrochloride | A-1331852 | Bax inhibitor peptide V5 | FX 1 | Gambogic Acid | TW-37 | UMI-77 | Acetate gossypol | HA14-1

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Molecular Formula ]:
C35H32FN5O4S2

[ Molecular Weight ]:
669.788

[ Exact Mass ]:
669.187988

[ LogP ]:
6.61

[ Index of Refraction ]:
1.716

[ Storage condition ]:
-20℃

Related Compounds