Details

Autor(en) / Beteiligte

• Strizki, Julie M.
• Xu, Serena
• Wagner, Nicole E.
• Wojcik, Lisa
• Liu, Jia
• Hou, Yan
• Endres, Michael
• Palani, Anandan
• Shapiro, Sherry
• Clader, John W.
• Greenlee, William J.
• Tagat, Jayaram R.
• McCombie, Stuart
• Cox, Kathleen
• Fawzi, Ahmad B.
• Chou, Chuan-Chu
• Pugliese-Sivo, Catherine
• Davies, Liza
• Moreno, Mary E.
• Ho, David D.
• Trkola, Alexandra
• Stoddart, Cheryl A.
• Moore, John P.
• Reyes, Gregory R.
• Baroudy, Bahige M.

Titel

SCH-C (SCH 351125), An Orally Bioavailable, Small Molecule Antagonist of the Chemokine Receptor CCR5, is a Potent Inhibitor of HIV-1 Infection in vitro and in vivo

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2001-10, Vol.98 (22), p.12718-12723

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• We describe here the identification and properties of SCH-C (SCH 351125), a small molecule inhibitor of HIV-1 entry via the CCR5 coreceptor. SCH-C, an oxime-piperidine compound, is a specific CCR5 antagonist as determined in multiple receptor binding and signal transduction assays. This compound specifically inhibits HIV-1 infection mediated by CCR5 in U-87 astroglioma cells but has no effect on infection of CXCR4-expressing cells. SCH-C has broad and potent antiviral activity in vitro against primary HIV-1 isolates that use CCR5 as their entry coreceptor, with mean 50% inhibitory concentrations ranging between 0.4 and 9 nM. Moreover, SCH-C strongly inhibits the replication of an R5-using HIV-1 isolate in SCID-hu Thy/Liv mice. SCH-C has a favorable pharmacokinetic profile in rodents and primates with an oral bioavailability of 50-60% and a serum half-life of 5-6 h. On the basis of its novel mechanism of action, potent antiviral activity, and in vivo pharmacokinetic profile, SCH-C is a promising new candidate for therapeutic intervention of HIV infection.