WT161 - 10mM in DMSO , CAS No.1206731-57-8

CAS: 1206731-57-8 Cat. No.: W420906 Fórmula: C₂₇H₃₀N₄O₃ Peso molecular: 458.55 PubChem CID: 44601455

CALIDAD & PUREZA 10mM in DMSO

Synonyms

Octanoic acid,8-​(hydroxyamino)​-​8-​oxo-​,2-​[[4-​(diphenylamino)​phenyl]​methylene]​hydrazide

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Descripción general

Information

WT161 is a potent, selective, and bioavailableHDAC6inhibitor withIC50 valuesof 0.4 nM, 8.35 nM and 15.4 nM for HDAC6, HDAC1 and HDAC2, respectively; shown to have >100-fold selectivity over other HDACs. WT161 inducesapoptosis.

Targets

HDAC6 (Cell-free assay); HDAC1 (Cell-free assay); HDAC2 (Cell-free assay) 0.4 nM; 8.35 nM; 15.4 nM

In vitro

WT161 selectively inhibits HDAC6 and dramatically increases levels of acetylated α-tubulin (Ac-α-tubulin) with little effect on global lysine acetylation. It induces accumulation of acetylated tubulin and cytotoxicity in multiple myeloma (MM) cells. WT161 as a single agent does not induce ER stress, the UPR, or ER stress-mediated apoptosis. Consistent with WT-161 mediated hyperacetylation and inhibition of hsp90 chaperone function, treatment with WT-161 increases the intracellular levels of polyubiuitylated proteins in the cultured MCL JeKo-1 and Z138 cells. WT-161 also dose-dependently depletes the levels of cyclin D1 in the cultured human Mantle Cell Lymphoma (MCL) cells. Treatment with WT-161 induces ER stress response in the MCL cells, demonstrated by increase in the protein levels of Glucose regulated protein (GRP) 78, phosphorylated eIF2 (eukaryotic initation factor 2) α, and induction of the pro-apoptotic transcription factor CHOP (CAAT/Enhancer Binding Protein Homologous Protein). WT161 triggers apoptotic cell death in MCF7, T47D, BT474, and MDA-MB231 cells, associated with decreased expression of EGFR, HER2, and ERα and downstream signaling.

In vivo

WT161 has reasonable half-life in mice (1.4 h) and drug exposure [maximum concentration (Cmax) = 18 mg/L]. It is well tolerated as a single agent. WT161 significantly inhibits in vivo MCF7 cell growth, associated with downregulation of ERα, in a murine xenograft model.

Cell Research(from reference)

Cell lines：MM.1S cells\xa0 

Concentrations：3 µM 

Incubation Time：16 h 

Especificaciones

Sinónimos

Octanoic acid,8-​(hydroxyamino)​-​8-​oxo-​,2-​[[4-​(diphenylamino)​phenyl]​methylene]​hydrazide

Especificaciones y pureza

10mM in DMSO

Mecanismos bioquímicos y fisiológicos

WT161 is a potent, selective, and bioavailable HDAC6 inhibitor with IC50 values of 0.4 nM, 8.35 nM and 15.4 nM for HDAC6, HDAC1 and HDAC2, respectively; shown to have >100-fold selectivity over other HDACs. WT161 induces apoptosis.

Condiciones de almacenamiento de almacenamiento

Store at -80°C

Enviado en

Dry ice packs + Cold packs

Este producto requiere envío en cadena de frío. Los servicios terrestres y otros servicios económicos no están disponibles.

Propiedades del producto

ALogP

5.406

Recuento HBD

2

Enlace rotable

12

Nombres e identificadores

Pubchem Sid

528768460

Sonrisas canónicas

C1=CC=C(C=C1)N(C2=CC=CC=C2)C3=CC=C(C=C3)C=NNC(=O)CCCCCCC(=O)NO

IUPAC Name

N'-hydroxy-N-[(E)-[4-(N-phenylanilino)phenyl]methylideneamino]octanediamide

InChIKey

KXWWYFKVBFUVIZ-SGWCAAJKSA-N

INCHI

1S/C27H30N4O3/c32-26(15-9-1-2-10-16-27(33)30-34)29-28-21-22-17-19-25(20-18-22)31(23-11-5-3-6-12-23)24-13-7-4-8-14-24/h3-8,11-14,17-21,34H,1-2,9-10,15-16H2,(H,29,32)(H,30,33)/b28-21+

Isómeros SMILES

C1=CC=C(C=C1)N(C2=CC=CC=C2)C3=CC=C(C=C3)/C=N/NC(=O)CCCCCCC(=O)NO

PubChem CID

44601455

Peso molecular

458.55

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic nitrogen compounds
    • Clase Organonitrogen compounds
      • Subclass Amines
        • Level5 Tertiary amines
          • Level6 Triarylamines

• Kingdom: Organic compounds
• Superclass: Organic nitrogen compounds
• Clase: Organonitrogen compounds
• Subclass: Amines
• Intermediate Tree Nodes: Tertiary amines
• Direct Parent: Triarylamines
• Alternative Parents: Aniline and substituted anilines Hydroxamic acids Amino acids and derivatives Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Tertiary aromatic amine - Aniline or substituted anilines - Benzenoid - Monocyclic benzene moiety - Hydroxamic acid - Amino acid or derivatives - Carboxylic acid derivative - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Carbonyl group - Aromatic homomonocyclic compound
• Descripción: This compound belongs to the class of organic compounds known as triarylamines. These are organic compounds containing a trialkylamine group, characterized by exactly three aryl groups bonded to the amino nitrogen.
• 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

Mecanismos de acción

Propiedades químicas y físicas

• DMSO (mg/ml) Solubilidad máxima: 86
• DMSO (mM) Solubilidad máxima: 187.5477047
• Agua (mg/ml) Solubilidad máxima: ＜1
• Peso molecular: 458.600 g/mol
• XLogP3: 4.900
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 12
• Exact Mass: 458.232 Da
• Monoisotopic Mass: 458.232 Da
• Topological Polar Surface Area: 94.000 Ų
• Heavy Atom Count: 34
• Formal Charge: 0
• Complexity: 603.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 1
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 1
• Covalently-Bonded Unit Count: 1