ABT-737CAS号: 852808-04-9分子式: C42H45ClN6O5S2分子量: 813.43描述纯度储存/保存方法别名外观可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)
产品描述 | |
描述 |
ABT-737是一种BH3模拟抑制剂,作用于Bcl-xL,Bcl-2和Bcl-w,无细胞试验中EC50分别为78.7 nM,30.3 nM和197.8 nM;但对Mcl-1, Bcl-B及Bfl-1没有抑制作用。 |
纯度 |
>98%
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储存/保存方法 |
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
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基本信息 | |
别名 |
ABT737;ABT 737
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外观 |
Light Yellow to Yellow solid
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可溶性/溶解性 |
DMSO : 50 mg/mL (61.47 mM)
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生物活性 | |
靶点 |
Bcl-2 ,Bcl-xL ,Bcl-w ,Bcl-B
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In vitro(体外研究) |
ABT-737 shows low activity to Bcl-B and no effects to Mcl-1 and BFL-1. ABT-737 is sensitive to HL60, KG1 and NB4 cells with IC50 of 50 nM, 80 nM and 80 nM, respectively. ABT-737 induces apoptosis in HL60 cells, which due to decreased Bcl-2/Bax heterodimerization and has no effect on cell cycle distribution. ABT-737 also induces cytochrome c release from purified mitochondria and promotes conformational changes in Bax that are associated with apoptosis. Resistant cells (Hela and MCF-7) can be sensitized to ABT-737 by approaches that down-regulate, destabilize, or inactivate Mcl-1. ABT-737 also causes Bax/BAK-dependent cytochrome c release only when Mcl-1 has been neutralized. ABT-737 displaces Bim from Bcl2’s BH3-binding pocket, allowing Bim to activate Bax, induce mitochondrial permeabilization, and rapidly commit the primary chronic lymphocytic leukemia (CLL) cells to death. Knockdown of Mcl-1 with siRNA sensitizes two resistant SCLC cell lines H196 and DMS114 to ABT-737 by enhancing the induction of apoptosis. Likewise, up-regulation of Noxa sensitizes H196 cells to ABT-737. ABT-737 inhibits proliferation and induces apoptosis in many SCLC cell lines including NCI-H889, NCI-H1963, NCI-H1417, NCI-H146 and etc. Bcl-2 and Noxa may contribute mechanistically to the cellular response to ABT-737 in NCI-H146 cells. A recent study shows that ABT-737 significantly induces apoptosis in HTLV-1 infected T-cell lines as well as in fresh ATLL cells.
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In vivo(体内研究) |
In aggressive leukemia model, ABT-737 suppresses the leukemia burden by 53% at the 30 mg/kg, with significantly extended survival of mice. ABT-737 does not induce significantly abnormalities in blood cell counts or serum chemistries. ABT-737 prolongs the survival of recipient mice transplanted with Bcl-2-transduced tumors. ABT-737 shows great antitumor activity in an ATLL mouse model at a dose of 100 mg/kg.
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分子结构图