title: A CD4 mimic as an HIV entry inhibitor: pharmacokinetics.
abstract: To date, several small molecules of CD4 mimics, which can suppress competitively the interaction between an HIV-1 envelope glycoprotein gp120 and a cellular surface protein CD4, have been reported as viral entry inhibitors. A lead compound 2 (YYA-021) with relatively high potency and low cytotoxicity has been identified previously by SAR studies. In the present study, the pharmacokinetics of the intravenous administration of compound 2 in rats and rhesus macaques is reported. The half-lives of compound 2 in blood in rats and rhesus macaques suggest that compound 2 shows wide tissue distribution and relatively high distribution volumes. A few hours after the injection, both plasma concentrations of compound 2 maintained micromolar levels, indicating it might have promise for intravenous administration when used combinatorially with anti-gp120 monoclonal antibodies.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Hashimoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Narumi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Otsuki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arai
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Harada
authors.forename: Nami
authors.initials: N
authors.lastname: Ohashi
authors.forename: Wataru
authors.initials: W
authors.lastname: Nomura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Shuzo
authors.initials: S
authors.lastname: Matsushita
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tamamura
mesh_terms: D061605:Administration, Intravenous; D000327:Adsorption; D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry* / Q000378:metabolism; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006207:Half-Life; D008253:Macaca mulatta; D018716:Molecular Mimicry; D015394:Molecular Structure; D010072:Oxamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D010880:Piperidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D015704:CD4 Antigens; D023581:HIV Fusion Inhibitors; D010880:Piperidines; C000591642:YYA-021; D010072:Oxamic Acid
keywords: CD4 mimic; HIV entry inhibitor; Intravenous administration; Pharmacokinetics