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ChemicalBook--->CAS DataBase List--->1206731-57-8

1206731-57-8

1206731-57-8 Structure

1206731-57-8 Structure
IdentificationBack Directory
[Name]

WT161
[CAS]

1206731-57-8
[Synonyms]

CS-2547
WT-III-161
WT161; WT 161
Octanoic acid, 8-(hydroxyamino)-8-oxo-, 2-[[4-(diphenylamino)phenyl]methylene]hydrazide
[Molecular Formula]

C27H30N4O3
[MDL Number]

MFCD31563598
[MOL File]

1206731-57-8.mol
[Molecular Weight]

458.55
Chemical PropertiesBack Directory
[density ]

1.15±0.1 g/cm3(Predicted)
[storage temp. ]

Store at -20°C
[solubility ]

DMF: 10 mg/ml; DMSO: 10 mg/ml; DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml
[form ]

A crystalline solid
[pka]

9.48±0.20(Predicted)
[color ]

White to off-white
Safety DataBack Directory
[Symbol(GHS) ]


GHS07
[Signal word ]

Warning
[Hazard statements ]

H302-H315-H319-H335
[Precautionary statements ]

P261-P264-P270-P271-P280-P301+P312-P330-P302+P352-P321-P304+P340-P305+P351+P338-P332+P313-P362+P364-P337+P313-P403+P233-P405-P501
Hazard InformationBack Directory
[Definition]

ChEBI: LSM-6269 is a tertiary amine.
[Biological Activity]

WT161 is a potent and selective HDAC6 inhibitor with IC50 values of 0.4 nM, 8.35 nM and 15.4 nM for HDAC6, HDAC1 and HDAC2, respectively, which is more than 100-fold selective for other HDACs.
[in vitro]

WT161 can selectively inhibit HDAC6 and significantly increase the level of acetylated α-tubulin, with little effect on the overall lysine acetylation. It is able to induce accumulation and toxicity of acetylated tubulin in multiple myeloma cells. WT161 alone did not induce ER stress response, UPR, or ER stress-related apoptosis. In cultured MCL JeKo-1 and Z138 cells, treatment with WT-161 increased intracellular ubiquitinated protein levels. WT-161 dose-dependently depletes cyclin D1 levels in cultured MCL cells (mantle cell lymphoma). Treatment of WT-161 also induced ER stress response in MCL cells-GRP78 protein level, phosphorylated eIF2α level increased, and pro-apoptotic transcription factor CHOP was induced. WT161 induced apoptotic cell death in MCF7, T47D, BT474 and MDA-MB231 cells, and decreased the expression of EGFR, HER2, ERα and downstream signals.

[in vivo]

WT161 has a reasonable half-life (1.4 hours) and drug exposure (Cmax=18 mg/L) in mice. It was well tolerated when administered as a single agent. It significantly inhibited the growth of MCF7 cells in vivo and down-regulated the expression of ERα in a xenograft tumor mouse model.

[target]

< td style="border-bottom: 1px dotted #ccc;padding: 5px;"> HDAC2
(Cell-free assay)
TargetValue
HDAC6
(Cell-free assay)
0.4 nM
HDAC1
(Cell-free assay)
8.35 nM
15.4 nM
[storage]

Store at -20°C
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