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
All
Chemical Reagents
Biomedicine
Organic raw materials
Inorganic chemical industry
intermediate
Agricultural chemicals
Auxiliaries and catalysts
Fragrances and Flavors
Dyes and Pigments
Daily chemical industry
WT161
CAS number：1206731-57-8 molecular formula：C27H30N4O3
overview
compound introduction
Specs
| Chinese alias | - | ||
| English alias | Octanoic acid,8-(hydroxyamino)-8-oxo-,2-[[4-(diphenylamino)phenyl]methylene]hydrazide | ||
| CAS number | 1206731-57-8 | molecular formula | C27H30N4O3 |
| molecular weight | 458.55 g/mol | Exact mass | ≥96% |
| PSA | 94.000 Ų | logp | 5.406 |
numbering system
No numbering system information yet
physicochemical properties
No physical and chemical property information yet
Safety information
No safety information yet
Production methods and uses
No production method and use information yet
Related
upstream information
No upstream information yet
downstream information
No downstream information yet
MSDS
Found 0 shareMSDS
