title: Authentic HIV-1 integrase inhibitors.
abstract: HIV-1 integrase (IN) is indispensable for HIV-1 replication and has become a validated target for developing anti-AIDS agents. In two decades of development of IN inhibition-based anti-HIV therapeutics, a significant number of compounds were identified as IN inhibitors, but only some of them showed antiviral activity. This article reviews a number of patented HIV-1 IN inhibitors, especially those that possess high selectivity for the strand transfer reaction. These compounds generally have a polar coplanar moiety, which is assumed to chelate two magnesium ions in the binding site. Resistance to those compounds, when given to patients, can develop as a result of IN mutations. We refer to those compounds as authentic IN inhibitors. Continued drug development has so far delivered one authentic IN inhibitor to the market (raltegravir in 2007). Current and future attention will be focused on the development of novel authentic IN inhibitors with the goal of overcoming viral resistance.
authors.affiliation: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, DHHS, Frederick, MD 21702, USA.
authors.forename: Chenzhong
authors.initials: C
authors.lastname: Liao
authors.forename: Christophe
authors.initials: C
authors.lastname: Marchand
authors.forename: Terrence R
authors.initials: TR
authors.lastname: Burke
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Marc C
authors.initials: MC
authors.lastname: Nicklaus
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000737:chemistry / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1