- 英文名称
- (S)-Morpholin-3-ylmethyl (4-((1-(3-fluorobenzyl)-1H-indazol-5-yl)amino)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)carbamate
- 分子式
- C27H27FN8O3
- 分子量
- 530.55
- 中文别名
- BMS-599626; AC480; 化合物BMS 599626; [4-[[1-(3-氟苄基)-1H-吲唑-5-基]氨基]-5-甲基吡咯并[2,1-F][1,2,4]三嗪-6-基]氨基甲酸(S)-吗啉-3-基甲酯; (S)-吗啉-3-基甲基 (4-((1-(3-氟苄基)-1H-吲唑-5-基)氨基)-5-甲基吡咯并[2,1-F][1,2,4]三嗪-6-基)氨基甲酸酯; BMS-599626; AC480; AC-480; cc-393; Carbamic acid, N-[4-[[1-[(3-fluorophenyl)methyl]-1H-indazol-5-yl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]-, (3S)-3-morpholinylmethyl ester; Carbamic acid, [4-[[1-[(3-fluorophenyl)methyl]-1H-indazol-5-yl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]-, (3S)-3-morpholinylmethyl ester (9CI); N-[4-[[1-[(3-Fluorophenyl)Methyl]-1H-indazol-5-yl]aMino]-5-Methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbaMic Acid (3S)-3-MorpholinylMethyl Ester; [(3S)-morpholin-3-yl]methyl N-[4-[[1-[(3-fluorophenyl)methyl]indazol-5-yl]amino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamate; (3S)-3-morpholinylmethyl ester; (S)-morpholin-3-ylmethyl-4-(1-(3-fluorobenzyl)-1H-indazol-5-ylamino)-5-methylpyrolo[1,2-f][1,2,4]triazin-6-ylcarbamate; (3S)-3-Morpholinylmethyl (4-{[1-(3-fluorobenzyl)-1H-indazol-5-yl]amino}-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)carbamate; [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6-yl]-carbamic acid; [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methyl-pyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid (3S)-3-morpholinylmethyl ester; [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-yl]carbamic acid (3S)-3-morpholinylmethyl ester
- 用途
- 表皮生长因子受体(EGFR)家族激酶抑制剂；选择性高效的HER1和HER2抑制剂，IC50分别为20 nM和30 nM，比对HER4效果强8倍左右，比对VEGFR2、c-Kit、Lck、MET等作用强100倍以上，Phase 1；选择性抑制重组HER1和HER2激酶的酶活性，IC50分别为20 nM和30 nM，对HER4的IC50为190 nM；是HER1的ATP竞争性抑制剂、HER2的ATP非竞争性抑制剂，Ki分别为2 nM和5 nM；抑制表达高水平HER1和/或HER2的肿瘤细胞增殖，对多种肿瘤细胞系的IC50在0.24 μM至0.94 μM之间，不会显著抑制不表达HER1或HER2的细胞增殖；通过促进周期再分配和抑制DNA修复，显著增强表达EGFR和Her2的HN-5细胞的放射敏感性；在体内按60 mg/kg到240 mg/kg剂量范围口服给药，抑制Sal2肿瘤生长，具有剂量依赖性，对人乳腺癌KPL-4移植瘤有有效抗癌活性，最大耐受剂量为180 mg/kg，对其他HER扩增或过量表达HER1的移植瘤模型有相似抗癌活性；是口服生物有效性的人表皮生长因子受体(HER)激酶HER1/HER2选择性抑制剂。
