Viracept (nelfinavir mesylate, AG1343): A potent, orally bioavailable inhibitor of HIV-1 protease
Viracept (nelfinavir mesylate, AG1343): A potent, orally bioavailable inhibitor of HIV-1 protease
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DOI：
10.1021/jm9704098
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发表时间：
1997-11-21
影响因子：
7.3
通讯作者：
Tatlock, JH
中科院分区：
文献类型：
--
作者：
Kaldor, SW;Kalish, VJ;Tatlock, JH
采用基于迭代结构的设计和口服药代动力学和抗病毒活性分析相结合，确定了HIV-1蛋白酶的非肽抑制剂AG1343 （Viracept，甲酸奈非那韦）。AG1343是一种有效的酶抑制剂（K-i = 2 nM）和抗病毒药物（HIV-1 ED50 = 14 nM）。酶- ag1343复合物的x射线共晶结构揭示了抑制剂的新型噻吩醚和酚酰胺取代基如何分别与HIV-1蛋白酶的S1和S2亚位相互作用。体内研究表明，AG1343在多种物种中均有良好的口服吸收，并在人体内具有良好的药代动力学特性。AG1343 （Viracept）最近被批准上市，用于治疗艾滋病。
Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (K-i = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively. In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans. AG1343 (Viracept) has recently been approved for marketing for the treatment of AIDS.