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Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist.
- Source :
-
ACS medicinal chemistry letters [ACS Med Chem Lett] 2011 Mar 31; Vol. 2 (6), pp. 450-4. Date of Electronic Publication: 2011 Mar 31 (Print Publication: 2011). - Publication Year :
- 2011
-
Abstract
- We report the identification of 13 (INCB3284) as a potent human CCR2 (hCCR2) antagonist. INCB3284 exhibited an IC50 of 3.7 nM in antagonism of monocyte chemoattractant protein-1 binding to hCCR2, an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 μM in inhibition of the hERG potassium current, a free fraction of 58% in protein binding, high selectivity over other chemokine receptors and G-protein-coupled receptors, and acceptable oral bioavailability in rodents and primates. In human clinical trials, INCB3284 exhibited a pharmacokinetic profile suitable for once-a-day dosing (T 1/2 = 15 h).
Details
- Language :
- English
- ISSN :
- 1948-5875
- Volume :
- 2
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- ACS medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 24900329
- Full Text :
- https://doi.org/10.1021/ml200030q