USP25/28 inhibitor AZ1

• CAT Number: I018162
• CAS Number: 2165322-94-9
• Molecular Formula: C17H16BrF4NO2
• Molecular Weight: 422.21
• Purity: ≥95%
• Synonyms: 2-[[5-bromo-2-[[4-fluoro-3-(trifluoromethyl)phenyl]methoxy]phenyl]methylamino]ethanol
• InChI: InChI=1S/C17H16BrF4NO2/c18-13-2-4-16(12(8-13)9-23-5-6-24)25-10-11-1-3-15(19)14(7-11)17(20,21)22/h1-4,7-8,23-24H,5-6,9-10H2
• InChIKey: ITHSFXDGKQYOED-UHFFFAOYSA-N
• SMILES: C1=CC(=C(C=C1COC2=C(C=C(C=C2)Br)CNCCO)C(F)(F)F)F

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].
USP25/28 inhibitor AZ1 (AZ1; 40 mg/kg; gavage; daily; for 7 days) protects from dextran sulfate sodium (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. 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;Trp53fl/fl (VP) mice. AZ1 treatment has minimal effect on tumorigenesis in the USP25-deficient background[1].

Reference

[1]. Wrigley JD, et al. Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating EnzymeSubfamily. ACS Chem Biol. 2017 Dec 15;12(12):3113-3125.
 [Content Brief]

[2]. Xiao-Meng Wang, et al. The deubiquitinase USP25 supports colonic inflammation and bacterial infection and promotes colorectal cancer. Nature Cancer volume 1, pages811–825(2020).