ARTICLE | Distillery Therapeutics


December 5, 2017 7:33 PM UTC

Cell culture and mouse studies suggest promoting CTNNB1 citrullination or PAD2 expression could help treat colorectal cancer. Screening of approved drugs in HEK cell-based assays of CTNNB1 signaling and cell line-based citrullination and binding assays in human colorectal cancer on the top hit identified Alinia nitazoxanide and a promoter of CTNNB1 citrullination that bound the CTNNB1-citrullinating enzyme PAD2 with a Kd value of 3.7 µM. In two human colorectal cancer cell lines, overexpression of PAD2 increased levels of citrullinated CTNNB1 and decreased colony formation compared with normal PAD2 expression. In one of the cell lines, Alinia decreased colony formation compared with vehicle. In a mouse model of colon cancer, Alinia decreased the number of intestinal microadenomas and macroadenomas. Next steps could include identifying and testing promoters of CTNNB1 citrullination in additional models of colorectal cancer...