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angelhunte

铁杆木虫 (正式写手)

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[求助] 辉瑞新上市的新药crizotinib的ALK酶抑制率是多少,如果有文献会追加100金币

辉瑞新上市的新药crizotinib的ALK酶抑制率是多少,如果有文献会追加100金币
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小冬瓜萱萱

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痴夷子皮: 金币+1, 热心奖励 2012-09-20 08:33:12
见附件图片数据

crizotinib.JPG

5楼2012-09-18 16:49:33
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songxiangen

金虫 (小有名气)

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感谢参与,应助指数 +1
痴夷子皮: 金币+1, 谢谢交流,欢迎常来哦。 2012-09-20 08:32:53
Crizotinib (PF-02341066) 的生物活性
Inhibitor of the catalytic activity of c-Met kinase and the NPM-ALK(nucleophosmin-anaplastic lymphoma kinase) fusion protein.[1] A t(2;5) chromosomal translocation resulting in expression of an oncogenic kinase fusion protein known as NPM-ALK has been implicated in the pathogenesis of anaplastic large-cell lymphoma (ALCL). [2]
After incubation with Crizotinib (PF-02341066), cells were washed once with HBSS supplemented with 1 mmol/L Na3VO4 and protein lysates were generated. Subsequently, phosphorylation of ALK was assessed by a sandwich ELISA method using an immobilized anti–total-ALK antibody and an anti–phospho-ALK antibody (pY1604) as a detec ion antibody.
Crizotinib (PF-02341066) inhibited NPM-ALKphosphorylation in Karpas299 or SU-DHL-1 ALCL cells (mean IC50 value=24 nM).
Crizotinib (PF-02341066) potently inhibited cell proliferation, which was associated with G1-S–phase cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells (IC50 values=30 nM) but not ALK-negative lymphoma cells. The induction of apoptosis was confirmed using terminal deoxyribonucleotide transferase–mediated nick-end labeling and Annexin V staining (IC50 values=25–50 nM). [3]

Crizotinib (PF-02341066) 参考文献
[1] Blood 2005;105: 2640-2653
[2] Oncogene 2001;20:5623-5637
[3] Mol Cancer Ther 2007;6:3314-3322

不知道对楼主有没有用
2楼2012-09-18 11:35:33
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angelhunte

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引用回帖:
2楼: Originally posted by songxiangen at 2012-09-18 11:35:33
Crizotinib (PF-02341066) 的生物活性
Inhibitor of the catalytic activity of c-Met kinase and the NPM-ALK(nucleophosmin-anaplastic lymphoma kinase) fusion protein. A t(2;5) chromosomal translocation r ...

细胞活性,我要的是酶活性,有报道说小于1nM,但不知道具体数据
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3楼2012-09-18 15:02:27
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小冬瓜萱萱

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★ ★ ★ ★ ★ ★ ★ ★ ★ ★
感谢参与,应助指数 +1
angelhunte: 金币+8, 有帮助, 至少说明您认真看过 2012-09-18 22:37:21
痴夷子皮: 金币+2, 谢谢交流,欢迎常来哦。 2012-09-20 08:32:59
还是我来应答吧!
crizotinib的ALK酶抑制率99%(1微摩尔浓度下),ALK酶抑制IC50小于1nm。
参考文献:Journal of Medicinal chemistry 2011, 54, 6342-6363(Table。5.)
4楼2012-09-18 16:41:24
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