A CD4 mimic as an HIV entry inhibitor: pharmacokinetics

  • Bioorg Med Chem. 2013 Dec 15;21(24):7884-9. doi: 10.1016/j.bmc.2013.10.005.
Chie Hashimoto  1 ,  Tetsuo Narumi ,  Hiroyuki Otsuki ,  Yuki Hirota ,  Hiroshi Arai ,  Kazuhisa Yoshimura ,  Shigeyoshi Harada ,  Nami Ohashi ,  Wataru Nomura ,  Tomoyuki Miura ,  Tatsuhiko Igarashi ,  Shuzo Matsushita ,  Hirokazu Tamamura
Affiliations
  • 1. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
PMID: 24189188 DOI: 10.1016/j.bmc.2013.10.005
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.

Keywords
CD4 mimic; HIV entry inhibitor; Intravenous administration; Pharmacokinetics.
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100039
    YYA-021
    98.96%, CD4-mimic HIV Entry Inhibitor
    target: HIV
    Research Areas: Infection