USP25 and 28 inhibitor AZ-1

Name	USP25/28 inhibitor AZ1； AZ1
Synonyms	AZ1 AZ-1 AZ 1 USP25 and 28 inhibitor AZ-1 2-((5-bromo-2-((4-fluoro-3-(trifluoromethyl)benzyl)oxy)benzyl)amino)ethanol Ethanol, 2-[[[5-bromo-2-[[4-fluoro-3-(trifluoromethyl)phenyl]methoxy]phenyl]methyl]amino]-
CAS	2165322-94-9

Molecular Formula	C17H16BrF4NO2
Molar Mass	422.21
Density	1.488±0.06 g/cm3(Predicted)
Boling Point	478.5±40.0 °C(Predicted)
Solubility	DMSO : 250 mg/mL (592.12 mM);H2O : < 0.1 mg/mL (insoluble)
pKa	14.74±0.10(Predicted)
Storage Condition	-20°C
In vivo study	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. 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. 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. AZ1 treatment has minimal effect on tumorigenesis in the USP25-deficient background. Animal Model: 12-week old male Usp25 +/+ and Usp25 -/- mice Dosage: 40 mg/kg Administration: Gavage; daily; for 7 days Result: Protected from dextran sulfate sodium (DSS)-induced weight loss and diarrhea and impaired colon shortening and potentiated the expression of proinflammatory cytokines and antibacterial peptides in colons of Usp25 -/- mice compared to control counterparts.