【摘要】：目的綜述c-ros原癌基因1(c-ros oncogene 1,ROS1)酪氨酸激酶的結(jié)構(gòu)和功能及其抑制劑的研究進(jìn)展。方法查閱近年來(lái)國(guó)內(nèi)外相關(guān)文獻(xiàn)47篇,對(duì)其進(jìn)行歸納總結(jié)和分析。結(jié)果 ROS1作為一個(gè)關(guān)鍵的跨膜受體蛋白酪氨酸激酶,控制細(xì)胞凋亡、生存、分化及增殖等多個(gè)細(xì)胞進(jìn)程,對(duì)多種惡性腫瘤的治療有重要作用,因此,開(kāi)發(fā)ROS1抑制劑具有重要的價(jià)值。2015年4月,克唑替尼(crizotinib)被美國(guó)FDA授予突破性藥物資格,用于ROS1陽(yáng)性非小細(xì)胞肺癌的潛在治療;隨后2-氨基嘧啶類(lèi)、4-芳氨基喹啉類(lèi)等化合物相繼被報(bào)道具有較強(qiáng)的ROS1激酶抑制活性,此外,一些選擇性ROS1抑制劑(如化合物12)也被開(kāi)發(fā)出來(lái)。結(jié)論盡管目前對(duì)ROS1選擇性抑制劑研究較少,但ROS1抑制劑仍具有良好的開(kāi)發(fā)前景。
[Abstract]:Objective to review the structure and function of c-ros proto-oncogene 1 (c-ros oncogene 1 rosl) tyrosine kinase and its inhibitors. Methods 47 literatures were reviewed, summarized and analyzed in recent years. Results as a key transmembrane receptor protein tyrosine kinase, ROS1 controls cell apoptosis, survival, differentiation and proliferation, and plays an important role in the treatment of various malignant tumors. The development of ROS1 inhibitors is of great value. In April 2015, (crizotinib) was awarded a breakthrough drug qualification by the United States FDA for the potential treatment of ROS1 positive non-small cell lung cancer (NSCLC). Subsequently, 2-aminopyrimidine, 4-arylaminoquinoline and other compounds have been reported to have strong ROS1 kinase inhibitory activity, in addition, some selective ROS1 inhibitors (such as compound 12) have also been developed. Conclusion although there are few studies on ROS1 selective inhibitors at present, ROS1 inhibitors still have a good prospect.
【作者單位】： 沈陽(yáng)藥科大學(xué)基于靶點(diǎn)的藥物設(shè)計(jì)與研究教育部重點(diǎn)實(shí)驗(yàn)室;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(81673308)
【分類(lèi)號(hào)】：R979.1
，

本文編號(hào)：2416199