Discovery of Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent Inhibitory Activities against Both Wild-type and Mutant ALK Kinases
文献类型：期刊论文
| 作者 | Song, Zilan1; Yang, Yanhong2; Liu, Zhiqing1; Peng, Xia2; Guo, Junfeng1; Yang, Xinying2; Wu, Kui1; Ai, Jing2 ; Ding, Jian2; Geng, Meiyu2
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| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2015-01-08 |
| 卷号 | 58期号:1页码:197-211 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm5005144 |
| 文献子类 | Article |
| 英文摘要 | We have developed a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) bearing a flexible amino acid side chain, different from the majority of the literature reported ALK inhibitors that often possess a structurally constrained arylpiperazine fragment or its equivalents in the solvent-interaction region. Extensive structural elaboration led to compound 15 possessing IC50 values of 2.7 and 15.3 nM, respectively, in the ALK wild-type and gate-keeper mutant L1196M enzymatic assays. This compound not only showed high proliferative inhibition against ALK-addicted cells across different oncogenic forms but also effectively suppressed several ALK secondary mutant cells, including the gate-keeper L1196M and F1174L. Significant antitumor efficacy was achieved in the ALK-driven SUP-M2 xenograft model. |
| WOS关键词 | ANAPLASTIC LYMPHOMA KINASE ; CELL LUNG-CANCER ; NON-HODGKINS-LYMPHOMA ; C-MET ; EXPERIMENTAL-MODELS ; THERAPEUTIC TARGET ; ANTITUMOR-ACTIVITY ; GENE ; IDENTIFICATION ; NEUROBLASTOMA |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000347743700012 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276676]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 |
| 通讯作者 | Ai, Jing |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Synthet Organ & Med Chem Lab, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Song, Zilan,Yang, Yanhong,Liu, Zhiqing,et al. Discovery of Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent Inhibitory Activities against Both Wild-type and Mutant ALK Kinases[J]. JOURNAL OF MEDICINAL CHEMISTRY,2015,58(1):197-211. |
| APA | Song, Zilan.,Yang, Yanhong.,Liu, Zhiqing.,Peng, Xia.,Guo, Junfeng.,...&Zhang, Ao.(2015).Discovery of Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent Inhibitory Activities against Both Wild-type and Mutant ALK Kinases.JOURNAL OF MEDICINAL CHEMISTRY,58(1),197-211. |
| MLA | Song, Zilan,et al."Discovery of Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent Inhibitory Activities against Both Wild-type and Mutant ALK Kinases".JOURNAL OF MEDICINAL CHEMISTRY 58.1(2015):197-211. |
入库方式： OAI收割
来源：上海药物研究所
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