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| Product Name: | AZ-1 | | Synonyms: | USP25 and 28 inhibitor AZ-1;Ethanol, 2-[[[5-bromo-2-[[4-fluoro-3-(trifluoromethyl)phenyl]methoxy]phenyl]methyl]amino]-;AZ-1;AZ 1;AZ1;USP25/28 inhibitor AZ1;2-((5-bromo-2-((4-fluoro-3-(trifluoromethyl)benzyl)oxy)benzyl)amino)ethanol;AZ-1;Deubiquitinase,USP-25/28 inhibitor AZ1,USP25/28 inhibitor AZ1,inhibit,AZ 1,Inhibitor,AZ-1,DUBs;2-((5-Bromo-2-((4-fluoro-3-(trifluoromethyl)benzyl)oxy)benzyl)amino)ethan-1-ol | | CAS: | 2165322-94-9 | | MF: | C17H16BrF4NO2 | | MW: | 422.21 | | EINECS: | | | Product Categories: | | | Mol File: | 2165322-94-9.mol |  |
| Boiling point | 478.5±40.0 °C(Predicted) | | density | 1.488±0.06 g/cm3(Predicted) | | storage temp. | Store at -20°C | | solubility | DMSO: ≥ 250 mg/mL (592.12 mM); Water: < 0.1 mg/mL (insoluble) | | form | Solid | | pka | 14.74±0.10(Predicted) | | color | White to off-white | | 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 | C(O)CNCC1=CC(Br)=CC=C1OCC1=CC=C(F)C(C(F)(F)F)=C1 |
| WGK Germany | WGK 3 | | Storage Class | 11 - Combustible Solids |
| Uses | 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]. | | Biological Activity | AZ1 is a potent and selective dual USP25 & USP28 deubiquitinase (DUBs) inhibitor (USP25/28 IC50 = 0.62/0.7 nM by Ub-Rh110 assay) th at induces HCT116 cellular c-Myc degradation (20-100 μM for 3h or 60 μM for 0.3-3h). AZ1 exhibits antiproliferation activity in cancer cultures (IC50 ≤20 μM; HCT116, HT29 and SW480) and anti-tumor efficacy in an orthotopic model of lung SCC tumours in mice in vivo (125 mg/kg or 375 mg/kg i.p. once every three days, 6 injections total). | | in vivo | USP25/28 inhibitor AZ1 (AZ1; 40mg/kg; gavage; daily; for 7days) protects from dextran sulfate sodium (DSS)-induced weight loss and diarrhea and impaired colon shortening[1].
USP25/28 inhibitor AZ1 (20mg/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 (20mg/kg/day; gavage; every 3days 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].
| Animal Model: | 12-week old male Usp25+/+ and Usp25-/- mice[1] | | Dosage: | 40mg/kg | | Administration: | Gavage; daily; for 7days | | 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.
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| | References | [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. DOI:10.1021/acschembio.7b00334
[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). |
| | AZ-1 Preparation Products And Raw materials |
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