"Old Dogs with New Tricks": exploiting alternative mechanisms of action and new drug design strategies for clinically validated HIV targets.
HIV-1 reverse transcriptase, protease and integrase have been recognized as clinically validated but still underexploited targets for antiretroviral treatment. Although a large number of inhibitors have been used in clinical trials, the rapid emergence of multiple drug-resistant strains requires the identification of not only novel classes of antiretroviral drugs that act via the unprecedented mechanism of action but also innovative drug discovery strategies towards these three important targets. This review summarizes and discusses current endeavours towards the discovery and development of novel inhibitors with alternative mechanisms of action, and also provides examples illustrating new methodologies in medicinal chemistry that contribute to the identification of novel antiretroviral agents.
Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, P. R. China. zhanpeng1982@163.com xinyongllab@163.com.
Dongwei
D
Kang
Yu'ning
Y
Song
Wenmin
W
Chen
Peng
P
Zhan
Xinyong
X
Liu
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans
D019380:Anti-HIV Agents