2. Academic Validation
  3. 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

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

  • Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12718-23. doi: 10.1073/pnas.221375398.
J M Strizki 1,  S Xu,  N E Wagner,  L Wojcik,  J Liu,  Y Hou,  M Endres,  A Palani,  S Shapiro,  J W Clader,  W J Greenlee,  J R Tagat,  S McCombie,  K Cox,  A B Fawzi,  C C Chou,  C Pugliese-Sivo,  L Davies,  M E Moreno,  D D Ho,  A Trkola,  C A Stoddart,  J P Moore,  G R Reyes,  B M Baroudy
Affiliations

Affiliation

  • 1 Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
PMID: 11606733 DOI: 10.1073/pnas.221375398
Abstract

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.

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