Novel Hybrids of (Phenylsulfonyl)furoxan and Anilinopyrimidine as Potent and Selective Epidermal Growth Factor Receptor Inhibitors for Intervention of Non-Small-Cell Lung Cancer
文献类型：期刊论文
| 作者 | Han, C; Huang, ZJ; Zheng, C; Wan, LD; Zhang, LW; Peng, SX; Ding, K; Ji, HB; Tian, JD; Zhang, YH |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2013 |
| 卷号 | 56期号:11页码:4738-4748 |
| 通讯作者 | Zhang, YH (reprint author), China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China.,ding_ke@gibh.ac.cn ; hbji@sibs.ac.cn ; zyhtgd@163.com |
| 英文摘要 | A series of hybrids (12a-k) from (phenylsulfonyl)furoxan and anilinopyrimidine were synthesized and biologically evaluated as epidermal growth factor receptor (EGFR) inhibitors for intervention of non-small-cell lung cancer (NSCLC). Compound 12k exhibited strong and selective EGFR L858R/T790M inhibitory activity (IC50 = 0.047 mu M) and displayed antiproliferative effects on EGFR mutation NSCLC cell lines HCC827 (del E746_A750) and H1975 (L858R/T790M) with IC50 values of 0.007 and 0.029 mu M, respectively. Additionally, 12k released high levels of NO in H1975 cells but not in normal human cells, and its activity was diminished by pretreatment with a NO scavenger. Furthermore, 12k induced apoptosis of H1975 and HCC827 cells more strongly than WZ4002 (1), inhibited EGFR downstream signaling in H1975 cells, and suppressed the nuclear factor-kappa B activation in H1975 cells, while 1 had no significant effects under the same conditions. Finally, 12k substantially inhibited tumor growth in an H1975 xenograft mouse model. Overall, 12k might be a promising candidate for the treatment of NSCLC. |
| 学科主题 | Pharmacology & Pharmacy |
| 类目[WOS] | Chemistry, Medicinal |
| 关键词[WOS] | TYROSINE KINASE INHIBITOR ; ANTIHEPATOCELLULAR CARCINOMA ACTIVITY ; OXIDE-RELEASING DERIVATIVES ; PHASE-II TRIAL ; NITRIC-OXIDE ; KAPPA-B ; EGFR ; RESISTANCE ; GEFITINIB ; MUTATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000320640900041 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/446]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Han, C,Huang, ZJ,Zheng, C,et al. Novel Hybrids of (Phenylsulfonyl)furoxan and Anilinopyrimidine as Potent and Selective Epidermal Growth Factor Receptor Inhibitors for Intervention of Non-Small-Cell Lung Cancer[J]. JOURNAL OF MEDICINAL CHEMISTRY,2013,56(11):4738-4748. |
| APA | Han, C.,Huang, ZJ.,Zheng, C.,Wan, LD.,Zhang, LW.,...&Zhang, YH.(2013).Novel Hybrids of (Phenylsulfonyl)furoxan and Anilinopyrimidine as Potent and Selective Epidermal Growth Factor Receptor Inhibitors for Intervention of Non-Small-Cell Lung Cancer.JOURNAL OF MEDICINAL CHEMISTRY,56(11),4738-4748. |
| MLA | Han, C,et al."Novel Hybrids of (Phenylsulfonyl)furoxan and Anilinopyrimidine as Potent and Selective Epidermal Growth Factor Receptor Inhibitors for Intervention of Non-Small-Cell Lung Cancer".JOURNAL OF MEDICINAL CHEMISTRY 56.11(2013):4738-4748. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。