Dataset Information

Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist.

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 ?M 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).

SUBMITTER: Xue CB

PROVIDER: S-EPMC4018154 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist.

Xue Chu-Biao CB Feng Hao H Cao Ganfeng G Huang Taisheng T Glenn Joseph J Anand Rajan R Meloni David D Zhang Ke K Kong Lingquan L Wang Anlai A Zhang Yingxin Y Zheng Changsheng C Xia Michael M Chen Lihua L Tanaka Hiroyuki H Han Qi Q Robinson D J DJ Modi Dilip D Storace Lou L Shao Lixin L Sharief Vaqar V Li Mei M Galya Laurine G LG Covington Maryanne M Scherle Peggy P Diamond Sharon S Emm Tom T Yeleswaram Swamy S Contel Nancy N Vaddi Kris K Newton Robert R Hollis Greg G Friedman Steven S Metcalf Brian B

ACS medicinal chemistry letters 20110331 6

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. I ...[more]

PMID: 24900329

Dataset Information

Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist.

Publications

Discovery of INCB3284, a Potent, Selective, and Orally Bioavailable hCCR2 Antagonist.

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