title: HIV-1 integrase inhibitors: a decade of research and two drugs in clinical trial.
abstract: AIDS is currently treated with a combination therapy of reverse transcriptase and protease inhibitors. Recently, the FDA approved a drug targeting HIV-1 entry into cells. There are currently no FDA approved drugs targeting HIV-1 integrase, though many scientists and drug companies are actively in pursuit of clinically useful integrase inhibitors. The objective of this review is to provide an update on integrase inhibitors reported in the last two years, including two novel inhibitors in early clinical trials, recently developed hydroxylated aromatics, natural products, peptide, antibody and oligonucleotide inhibitors. Additionally, the proposed mechanism of diketo acid inhibition is reviewed.
authors.affiliation: Laboratory of Molecular Pharmacology, CCR, NCI, NIH, Building 37, Room 5068, Bethesda, MD 20892, USA.
authors.forename: Allison A
authors.initials: AA
authors.lastname: Johnson
authors.forename: Christophe
authors.initials: C
authors.lastname: Marchand
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
mesh_terms: D000090:Acetoacetates / Q000737:chemistry / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D001685:Biological Factors / Q000737:chemistry / Q000494:pharmacology; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology; D002986:Clinical Trials as Topic; D005663:Furans; D019427:HIV Integrase / Q000737:chemistry / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000472:pathogenicity; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013386:Succinates / Q000737:chemistry / Q000494:pharmacology; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles
chemical_list: C400757:1-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)propenone; D000090:Acetoacetates; D019380:Anti-HIV Agents; D001685:Biological Factors; D002109:Caffeic Acids; D005663:Furans; D019428:HIV Integrase Inhibitors; D007211:Indoles; C403887:L 708906; C403886:L 731988; D009841:Oligonucleotides; D011758:Pyrroles; D018894:Reverse Transcriptase Inhibitors; C451733:S 1360; D013386:Succinates; D013777:Tetrazoles; D014230:Triazoles; D019427:HIV Integrase; C100435:chicoric acid