1206731-57-8

Basic information

• Product Name: WT161
• Synonyms: CS-2547;WT-III-161;WT161; WT 161;Octanoic acid, 8-(hydroxyamino)-8-oxo-, 2-[[4-(diphenylamino)phenyl]methylene]hydrazide
• CAS NO: 1206731-57-8
• Molecular Formula: C27H30N4O3
• Molecular Weight: 458.5521
• Product Categories: API
• Mol File: 1206731-57-8.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Density: 1.15±0.1 g/cm3(Predicted)
• PKA: 9.48±0.20(Predicted)
• CAS DataBase Reference: WT161(CAS DataBase Reference)
• NIST Chemistry Reference: WT161(1206731-57-8)
• EPA Substance Registry System: WT161(1206731-57-8)

Safety Data

• Hazardous Substances Data: 1206731-57-8(Hazardous Substances Data)

Usage

General Description

WT161 is a novel chemical compound that acts as a potent and selective inhibitor of the STT3A subunit of the oligosaccharyltransferase complex. This complex is involved in the N-linked glycosylation of proteins and plays a crucial role in protein folding and stability. By targeting the STT3A subunit, WT161 has been shown to disrupt glycosylation and induce ER stress, leading to the selective inhibition of cancer cell growth. Therefore, WT161 has potential as a therapeutic agent for cancer treatment, and further research into its mechanism of action and potential side effects is warranted.

Upstream product

• 4181-05-9 4-(diphenylamino)benzaldehyde 

Relevant articles and documents

Discovery of selective small-molecule HDAC6 inhibitor for overcoming proteasome inhibitor resistance in multiple myeloma

Multiple myeloma (MM) has proven clinically susceptible to modulation of pathways of protein homeostasis. Blockade of proteasomal degradation of polyubiquitinated misfolded proteins by the proteasome inhibitor bortezomib (BTZ) achieves responses and prolongs survival in MM, but long-term treatment with BTZ leads to drug-resistant relapse in most patients. In a proof-of-concept study, we previously demonstrated that blocking aggresomal breakdown of polyubiquitinated misfolded proteins with the histone deacetylase 6 (HDAC6) inhibitor tubacin enhances BTZ-induced cytotoxicity in MM cells in vitro. However, these foundational studies were limited by the pharmacologic liabilities of tubacin as a chemical probe with only in vitro utility. Emerging from a focused library synthesis, a potent, selective, and bioavailable HDAC6 inhibitor, WT161, was created to study the mechanism of action of HDAC6 inhibition in MM alone and in combination with BTZ. WT161 in combination with BTZ triggers significant accumulation of polyubiquitinated proteins and cell stress, followed by caspase activation and apoptosis. More importantly, this combination treatment was effective in BTZ-resistant cells and in the presence of bone marrow stromal cells, which have been shown to mediate MM cell drug resistance. The activity of WT161 was confirmed in our human MM cell xenograft mouse model and established the framework for clinical trials of the combination treatment to improve patient outcomes in MM.