L11   Development of CCR5 Antagonists as a New Class of Anti-HIV Therapeutic

Gregory Reyes
Schering-Plough Res. Inst., Kenilworth, NJ

The elucidation of chemokine receptors CCR5 and CXCR4 as co-receptors required for HIV entry into cells provides a new cell-based, non-viral encoded target for the development of antiviral compounds that would selectively prevent viral fusion/entry. Previous work has established that intervention at the point of virus entry might be viable as part of a combined antiviral therapeutic regimen given the demonstration that both infected cells and virus present in plasma have short half lives. We have succeeded in identifying and optimizing small molecule antagonists to the CCR5 chemokine receptor. Several classes of molecules emerged from our high throughput screening effort and medicinal chemistry optimization has led to our lead clinical candidate, SCH C. The compound is a potent antagonist of RANTES binding (Ki ~3nM), shows sub-nM activity in viral entry assays and has excellent potency versus a range of primary viral isolates. Initial safety and pharmacokinetic data will be presented for SCH C. Further work by the group has led to the identification of even more potent antagonists of CCR5 and the status of these advances will be described.

Session 62. Symposium

Viral Reservoirs

Wednesday, 2:00-4:00pm

Ballroom I-V