USP25/28 inhibitor AZ1

USP25/28 inhibitor AZ1 (AZ1) is an orally active, selective, noncompetitive, dual ubiquitin specific protease (USP) 25/28 inhibitor with IC₅₀s of 0.7 μM and 0.6 μM, respectively. USP25/28 inhibitor AZ1 attenuates colitis and tumorigenesis in the mice model^[1][2]. IC50 & Target:IC50: 0.7 μM (USP25) and 0.6 μM (USP28)^[1] In Vivo:USP25/28 inhibitor AZ1 (AZ1; 40 mg/kg; gavage; daily; for 7 days) protects from Dextran sulfate sodium salt (HY-116282C) (DSS)-induced weight loss and diarrhea and impaired colon shortening^[1].
USP25/28 inhibitor AZ1 (20 mg/kg/day; gavage; 6 times a week in the 1, 3, 6 weeks) treatment significantly reduces tumor numbers in colons. Expression of Wnt-related genes and levels of pSTAT3 are decreased and levels of SOCS3 are increased in tumors. USP25/28 inhibitor AZ1 gavage does not alleviate DSS-induced colitis in Usp25^-/- mice or the spontaneous colitis of Il10^-/- mice^[1].
USP25/28 inhibitor AZ1 (20 mg/kg/day; gavage; every 3 days from 13-20 weeks) significantly inhibits tumorigenesis in the colon and prolonged the survival of AOM/Vil-Cre;Trp53^fl/fl (VP) mice. USP25/28 inhibitor AZ1 treatment has minimal effect on tumorigenesis in the USP25-deficient background^[1].