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angelhunte
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3Â¥2012-09-18 15:02:27
songxiangen
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Crizotinib (PF-02341066) µÄÉúÎï»îÐÔ 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¨Ctotal-ALK antibody and an anti¨Cphospho-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¨Cphase 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¨Cmediated nick-end labeling and Annexin V staining (IC50 values=25¨C50 nM). [3] Crizotinib (PF-02341066) ²Î¿¼ÎÄÏ× [1] Blood 2005;105: 2640-2653 [2] Oncogene 2001;20:5623-5637 [3] Mol Cancer Ther 2007;6:3314-3322 ²»ÖªµÀ¶ÔÂ¥Ö÷ÓÐûÓÐÓà |
2Â¥2012-09-18 11:35:33
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angelhunte: ½ð±Ò+8, ¡ïÓаïÖú, ÖÁÉÙ˵Ã÷ÄúÈÏÕæ¿´¹ý 2012-09-18 22:37:21
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angelhunte: ½ð±Ò+8, ¡ïÓаïÖú, ÖÁÉÙ˵Ã÷ÄúÈÏÕæ¿´¹ý 2012-09-18 22:37:21
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»¹ÊÇÎÒÀ´Ó¦´ð°É£¡ crizotinibµÄALKøÒÖÖÆÂÊ99%£¨1΢Ħ¶ûŨ¶ÈÏ£©£¬ALKøÒÖÖÆIC50СÓÚ1nm¡£ ²Î¿¼ÎÄÏ×£ºJournal of Medicinal chemistry 2011£¬ 54£¬ 6342-6363£¨Table¡£5.£© |
4Â¥2012-09-18 16:41:24
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5Â¥2012-09-18 16:49:33













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