BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: CC chemokine receptor 9 (CCR9; CDw199)

April 21, 2016 7:00 AM UTC

Cell line and mouse studies identified dioxoisoindoline-based CCR9 antagonists that could help treat colitis. Chemical synthesis of dioxoisoindoline analogs and testing in a human cell-based binding assay identified three compounds that bound to CCR9 with Ki values of 6-13 nM. In two mouse models of chemical-induced colitis, the compounds decreased weight loss, stool blood, diarrhea and other measures of disease severity compared with vehicle. In mice, the compounds had half-lives of 0.62, 1.28 and 1.05 hours, respectively. Next steps could include optimizing and testing the compounds in additional models of colitis...