目前抗血管生成治療是抗腫瘤研究的熱點。血管內(nèi)皮生長因子（VEGF）是刺激血管生成的重要因子之一，血管內(nèi)皮生長因子受體（VEGFR）在腫瘤新生血管中高表達，因此成為腫瘤靶向治療的理想靶點。以VEGF、VEGFR為靶點的抗腫瘤藥物除了常見的單克隆抗體藥物阿伐斯汀外，小分子抑制劑舒尼替尼、索拉非尼等也已經(jīng)廣泛使用；另外，一些具有上市潛力的藥物，如范得他尼、西地尼布、瓦他拉尼、阿西替尼等也值得關(guān)注。已上市和正在進行臨床研究的VEGFR小分子抑制劑按結(jié)構(gòu)大致分為6類：喹啉及喹唑啉類、噠嗪類、吲唑類、咪唑和吡咯嘧啶類、吲哚類和其他結(jié)構(gòu)等。對VEGF、VEGFR的生物學功能，其代表性的小分子抑制劑研究進行綜述。

Recently, the anti-angiogenic therapy is a hot focus for antitumor research. The vascular endothelial growth factor (VEGF) is one of the most important angiogenesis stimulators. The vascular endothelial growth factor receptor (VEGFR) is high expressed in the new vessels of tumor tissues, so the antiangiogenic therapy aiming at VEGFR becomes an ideal treatment method. Besides the monoclonal antibody drug Avastin, the small-molecule inhibitors such as sunitinib and sorafenib are already widely used in the antitumor therapy aimed at VEGF and VEGFR. Moreover, it is also worth attention to some clinical drugs with potential market acceptance (vandetanib, cediranib, vatalanib, axtinib, et al). For the drugs on the market and VEGFR-targeted small-molecule inhibitors in clinical study, we roughly divided them into six kinds on structures including quinoline and quinazoline, pyridazine, indazole, imidazole, pyrrolo[2,3-d]pyrimidine, indole, and others. The recent studies of the biologyical function of VEGF and VEGFR and their representative small-molecule inhibitors are reviewed in this paper.

國家重大新藥創(chuàng)制專項（2011ZX09401-009）