VLX1570 - Moligand™, 10mM in DMSO , Inhibitor of ubiquitin specific peptidase 14, CAS No.1431280-51-1, Inhibitor of ubiquitin specific peptidase 14

CAS: 1431280-51-1 Cat. No.: V421591 Molecular Weight: 469.39 PubChem CID: 118989091

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

4H-​Azepin-​4-​one,3,​5-​bis[(4-​fluoro-​3-​nitrophenyl)​methylene]​hexahydro-​1-​(1-​oxo-​2-​propen-​1-​yl)​-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

VLX1570 VLX1570 is a competitive inhibitor of proteasome DUB activity, with an IC50 of ~10 μM in vitro.

Targets

DUB (Cell-free assay) ~10 μM

In vitro

VLX1570 is an analogue of b-AP15 that shows higher potency and improved solubility. VLX1570 preferentially inhibits proteasomal DUB activity while not inhibiting the activities of a panel of non-proteasomal DUBs. VLX1570 binds to and inhibits the activity of ubiquitin-specific protease-14 (USP14) with comparatively weaker inhibitory activity towards UCHL5 (ubiquitin-C-terminal hydrolase-5). Treatment of multiple myeloma cells with VLX1570 induces the accumulation of proteasome-bound high molecular weight polyubiquitin conjugates and an apoptotic response. VLX1570 induces the expression of the chaperone HSP70B′, the oxidative stress marker Hmox-1, and the ER stress marker XBP-1s. VLX1570 is retained in cells after removal of drug and that USP14 was engaged by drug 17\u2009hours after wash-out, as evidenced by thermal stabilization and persistent enzyme inhibition.

In vivo

VLX1570 is an inhibitor of proteasome DUB activity currently in clinical trials for relapsed multiple myeloma. Treatment with VLX1570 is found to lead to extended survival in xenograft models of multiple myeloma. The in vivo IC50 for inhibition of proteasome DUB activity and induction of apoptosis is <1\u2009μM, with multiple myeloma cells showing greater levels of sensitivity compared to other tumor types. The lower IC50 for activity in vivo is presumably due to rapid drug uptake and enrichment in cells.

Cell Research(from reference)

Cell lines：OPM-2\u2009MM cells 

Concentrations：0.5 μM 

Incubation Time：3 h 

Specifications

Synonyms

4H-​Azepin-​4-​one, 3, ​5-​bis[(4-​fluoro-​3-​nitrophenyl)​methylene]​hexahydro-​1-​(1-​oxo-​2-​propen-​1-​yl)​-

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

VLX1570 is a competitive inhibitor of proteasome DUB activity, with an IC50 of ~10\u2009μM in vitro.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Inhibitor of ubiquitin specific peptidase 14

Product Properties

• ALogP: 4.385
• Rotatable Bond: 5

Names and Identifiers

• Pubchem Sid: 528767643
• Canonical Smiles: C=CC(=O)N1CCC(=CC2=CC(=C(C=C2)F)[N+](=O)[O-])C(=O)C(=CC3=CC(=C(C=C3)F)[N+](=O)[O-])C1
• IUPAC Name: (3Z,5Z)-3,5-bis[(4-fluoro-3-nitrophenyl)methylidene]-1-prop-2-enoylazepan-4-one
• InChIKey: SCKXBVLYWLLALY-CQRYCMKKSA-N
• 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-
• PubChem CID: 118989091
• MeSH Entry Terms: VLX1570
• Molecular Weight: 469.39

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Benzene and substituted derivatives
      • Subclass Nitrobenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Nitrobenzenes
• Intermediate Tree Nodes: Not available
• Direct Parent: Nitrobenzenes
• Alternative Parents: Nitroaromatic compounds Fluorobenzenes Azepanes Aryl fluorides Tertiary carboxylic acid amides Acrylic acids and derivatives Cyclic ketones Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Azacyclic compounds Organopnictogen compounds Organonitrogen compounds Organofluorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Nitrobenzene - Nitroaromatic compound - Halobenzene - Fluorobenzene - Azepane - Aryl halide - Aryl fluoride - Acrylic acid or derivatives - Tertiary carboxylic acid amide - Organic nitro compound - Cyclic ketone - C-nitro compound - Ketone - Carboxamide group - Azacycle - Organoheterocyclic compound - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Allyl-type 1,3-dipolar organic compound - Organic oxoazanium - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Carbonyl group - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as nitrobenzenes. These are compounds containing a nitrobenzene moiety, which consists of a benzene ring with a carbon bearing a nitro group.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Associated Targets(Human)

USP14 Tchem Ubiquitin carboxyl-terminal hydrolase 14 (0 Activities)

Discover Target: USP14

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Chemical and Physical Properties

• DMSO(mg / mL) Max Solubility: 93
• DMSO(mM) Max Solubility: 198.1294872
• Water(mg / mL) Max Solubility: ＜1