CT1170 is a potent, small molecule inhibitor of deubiquitinase OTUD5 with IC50 of 147.6 nM in DUB assays, enhances the ubiquitination modification on STAT1 and STAT2.
CT1170 blocks IFNγ-induced up-regulation of STAT1 and 2, and the expression of Ccl8 in MC38 cells.
CT1170 effectively blocks IFNγ signaling as evidenced by the diminished upregulation of all three ISGF3 components in colon organoids derived from one IBD patient, suppresses IFNγ-induced upregulation of STAT1 and 2.
CT1170 also induces downregulation of OTUD5 in murine and human intestinal cell lines as well as in human colon organoids, likely because OTUD5 acts as its own deubiquitinase.
CT1170 (5, 10, and 15 mg/kg, oral gavage, twice daily) alleviates DSS-induced colitis in male adult mice, prevented tissue destruction induced by DSS in a dose-dependent manner.
CT1170 (5 mg/kg, b.i.d.) suppresses colitis-associated tumorigenesis.