title: Novel HIV-1 integrase inhibitors derived from quinolone antibiotics.
abstract: The viral enzyme integrase is essential for the replication of human immunodeficiency virus type 1 (HIV-1) and represents a remaining target for antiretroviral drugs. Here, we describe the modification of a quinolone antibiotic to produce the novel integrase inhibitor JTK-303 (GS 9137) that blocks strand transfer by the viral enzyme. It shares the core structure of quinolone antibiotics, exhibits an IC50 of 7.2 nM in the strand transfer assay, and shows an EC50 of 0.9 nM in an acute HIV-1 infection assay.
authors.affiliation: Central Pharmaceutical Research Institute, JT Inc., 1-1 Murasaki-cho, Takatsuki, Osaka, 569-1125, Japan.
authors.forename: Motohide
authors.initials: M
authors.lastname: Sato
authors.forename: Takahisa
authors.initials: T
authors.lastname: Motomura
authors.forename: Hisateru
authors.initials: H
authors.lastname: Aramaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamashita
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawakami
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Watanabe
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Yamataka
authors.forename: Satoru
authors.initials: S
authors.lastname: Ikeda
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kodama
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shinkai
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004279:DNA, Viral / Q000737:chemistry; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D015363:Quinolones; C509700:elvitegravir; D019427:HIV Integrase