| Identification | Back Directory | [Name]
VLX1570 | [CAS]
1431280-51-1 | [Synonyms]
VLX1570
CS-2226
VLX1570 (VLX 1570
4H-Azepin-4-one, 3,5-bis[(4-fluoro-3-nitrophenyl)methylene]hexahydro-1-(1-oxo-2-propen-1-yl)- | [Molecular Formula]
C23H17F2N3O6 | [MDL Number]
MFCD28502165 | [MOL File]
1431280-51-1.mol | [Molecular Weight]
469.39 |
| Chemical Properties | Back Directory | [storage temp. ]
Store at -20°C | [solubility ]
DMF:25.0(Max Conc. mg/mL);53.26(Max Conc. mM)
DMF:PBS (pH 7.2) (1:2):0.3(Max Conc. mg/mL);0.64(Max Conc. mM)
DMSO:47.0(Max Conc. mg/mL);100.13(Max Conc. mM) | [form ]
A crystalline solid | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Description]
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. | [Uses]
VLX1570 is a proteasome deubiquitinase inhibitor. It also exhibits antineoplastic activities. | [in vivo]
VLX1570 (3?mg/kg) significantly decreases tumor growth in mice bearing KMS-11 multiple myeloma cells[2]. VLX1570 (4.4?mg/kg, i.p.) markedly suppresses tumor growth, without obvious weight loss and other signs of systemic toxicity in the Waldenstrom macroglobulinemia (WM)-bearing mice[3]. | [References]
[1] XIN WANG. Synthesis and Evaluation of Derivatives of the Proteasome Deubiquitinase Inhibitor b-AP15[J]. Chemical Biology & Drug Design, 2015, 86 5: 1036-1048. DOI: 10.1111/cbdd.12571
[2] XIN WANG. The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells.[J]. Scientific Reports, 2016: 26979. DOI: 10.1038/srep26979
[3] CHIA-CHUAN CHO. Drug Repurposing for the SARS-CoV-2 Papain-Like Protease[J]. ChemMedChem, 2021, 17 1. DOI: 10.1002/cmdc.202100455 |
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