Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation.
Cilengitide: the first anti-angiogenic small molecule drug candidate design, synthesis and clinical evaluation.
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DOI：
10.2174/187152010794728639
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发表时间：
2010-12
影响因子：
2.8
通讯作者：
Kessler H
中科院分区：
文献类型：
--
作者：
Mas-Moruno C;Rechenmacher F;Kessler H
Cilengitide是一种环状RGD五肽，目前处于治疗胶质母细胞瘤的临床III期和治疗其他几种肿瘤的II期。该药物是首个靶向整合素αvβ3、αvβ5和α5β1的抗血管生成小分子药物。它是由我们在90年代早期通过一种新颖的程序开发出来的，空间筛选。该策略产生了第一个超活性αvβ3抑制剂c(RGDfV)，其活性比线性参考肽提高100至1000倍，并且对血小板受体αIIbβ3具有高选择性。该环肽随后通过一个肽键的n -甲基化修饰，产生更大的c（RGDf(NMe)V）拮抗活性。这种肽后来被命名为Cilengitide，目前由德国默克雪兰诺公司开发为药物。本文介绍了西伦吉肽的化学发展、其活性的生化背景以及目前临床试验的简要综述。通过与“经典”抗癌疗法的结合，癌症治疗中抗血管生成的积极作用可以进一步增强。这方面的几个临床试验正在调查中。
Cilengitide, a cyclic RGD pentapeptide, is currently in clinical phase III for treatment of glioblastomas and in phase II for several other tumors. This drug is the first anti-angiogenic small molecule targeting the integrins αvβ3, αvβ5 and α5β1. It was developed by us in the early 90s by a novel procedure, the spatial screening. This strategy resulted in c(RGDfV), the first superactive αvβ3 inhibitor (100 to 1000 times increased activity over the linear reference peptides), which in addition exhibited high selectivity against the platelet receptor αIIbβ3. This cyclic peptide was later modified by N-methylation of one peptide bond to yield an even greater antagonistic activity in c(RGDf(NMe)V). This peptide was then dubbed Cilengitide and is currently developed as drug by the company Merck-Serono (Germany). This article describes the chemical development of Cilengitide, the biochemical background of its activity and a short review about the present clinical trials. The positive anti-angiogenic effects in cancer treatment can be further increased by combination with “classical” anti-cancer therapies. Several clinical trials in this direction are under investigation.
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影响因子：
15
作者：
BACH, AC;EYERMANN, CJ;DEGRADO, WF
通讯作者：
DEGRADO, WF
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
用环状RGD肽抑制α-NU整联蛋白会损害体内实体瘤的血管生成，生长和转移。
影响因子：
8.8
作者：
Buerkle, M A;Pahernik, S A;Sutter, A;Jonczyk, A;Messmer, K;Dellian, M
通讯作者：
Dellian, M
影响因子：
16.6
作者：
Biron, Eric;Chatterjee, Jayanta;Kessler, Horst
通讯作者：
Kessler, Horst