VLX1570

VLX1570 is an inhibitor of 19S proteasomal deubiquitinases with IC50 values of 6.4 and 13 µM for deubiquitinase activity in vitro using Ub-rhodamine and Ub-AMC, respectively, as substrates. It is selective for proteasomal deubiquitinases over a panel of deubiquitinases at 20 µM, but inhibits USP5 by greater than 50%, and over a panel of 211 kinases at 10 µM, but inhibits Cdk4 by 77%. VLX1570 binds to and inhibits recombinant ubiquitin-specific protease 14 (USP14) and ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5) in vitro, and inhibits the USP14 and UCHL5 activity of purified 19S proteasomes when used at a concentration of 50 µM. It inhibits the proliferation of KMS-11, RPMI-8226, OPM-2, and OPM-2-BZR multiple myeloma cells (IC50s = 43, 74, 126, and 191 nM, respectively), as well as induces apoptosis and increases the accumulation of polyubiquitinated proteins. VLX1570 (3 mg/kg per day for 10 days) increases survival and reduces tumor growth in KMS-11-LUC2 and RPMI-8226 mouse xenograft models, respectively.Formal Name: 3,5-bis[(4-fluoro-3-nitrophenyl)methylene]hexahydro-1-(1-oxo-2-propen-1-yl)-4H-azepin-4-one. CAS Number: 1431280-51-1. Molecular Formula: C23H17F2N3O6. Formula Weight: 469.4. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMF:PBS (pH 7.2) (1:2): 0.3 mg/ml, DMSO: 16 mg/ml, Ethanol: Partially soluble. lambdamax: 296 nm. SMILES: O=C(/C(CCN(C(C=C)=O)C/1)=C/C2=CC([N+]([O-])=O)=C(F)C=C2)C1=C\C3=CC=C(F)C([N+]([O-])=O)=C3. InChi Code: InChI=1S/C23H17F2N3O6/c1-2-22(29)26-8-7-16(9-14-3-5-18(24)20(11-14)27(31)32)23(30)17(13-26)10-15-4-6-19(25)21(12-15)28(33)34/h2-6,9-12H,1,7-8,13H2/b16-9+,17-10+. InChi Key: SCKXBVLYWLLALY-CZCYGEDCSA-N.