330450-45-8

Basic information

• Product Name: b-AP15
• Synonyms: b-AP15;NSC-687852;(3Z,5E)-1-Acryloyl-3,5-bis(4-nitrobenzylidene)-piperidin-4-one
• CAS NO: 330450-45-8
• Molecular Formula: C22H17N3O6
• Molecular Weight: 419.4
• Mol File: 330450-45-8.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: b-AP15(CAS DataBase Reference)
• NIST Chemistry Reference: b-AP15(330450-45-8)
• EPA Substance Registry System: b-AP15(330450-45-8)

Safety Data

• Hazardous Substances Data: 330450-45-8(Hazardous Substances Data)

Usage

Enzyme inhibitor

This deubiquitinase inhibitor (FW = 421.31 g/mol; CAS 1009817-63-3), also named 3,5-bis[ (4-nitrophenyl) methylene]-1- (1-oxo-2-propen-1-yl) - (3E,5E) -4-piperidinone, targets two proteasome-associated ubiquitin carboxyl-terminal hydrolase-14, or USP14, and Ubiquitin Carboxyl-terminal Hydrolase isozyme L5 UCHL5, IC50 = 2.1 μM, resulting in a rapid accumulation of high-molecular-weight ubiquitin conjugates and functional shutdown of proteasome. Interestingly, b-AP15 displays several differences with respect to bortezomib including insensitivity to over-expression of the anti-apoptotic mediator Bcl-2 and anti-tumor activity in solid tumor models. Inhibition of DUBs blocked the processing and release of interleukin IL-1β in both mouse and human macrophages. DUB activity was necessary for inflammasome association as DUB inhibition also impaired ASC oligomerization and caspase-1 activation without directly blocking caspase- 1 activity. These data reveal the requirement for DUB activity in a key reaction of the innate immune response and highlight the therapeutic potential of DUB inhibitors for chronic auto-inflammatory diseases. (See also Bortezomib, Eeeyarestatin I)

Upstream product

• 814-68-6 acryloyl chloride 
• 919091-63-7 (3E,5E)-3,5-bis[(4-nitrophenyl)methylidene]piperidin-4-one 
• 1349003-94-6 3,5-bis-4-nitrobenzylidenepiperidin-4-one hydrochloride 
• 555-16-8 4-nitrobenzaldehdye 
• 41979-39-9 4-piperidone hydrochloride 

Relevant articles and documents

Design, synthesis and tumour-selective toxicity of novel 1-[3-{3,5-bis(Benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes and related quaternary ammonium salts

A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes 3a–h and related quaternary ammonium salts 4a–h were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells

Curcumin-inspired cytotoxic 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones: A novel group of topoisomerase II alpha inhibitors

Three series of novel 3,5-bis(arylmethylene)-1-(N-(ortho-substituted aryl)maleamoyl)-4-piperidones, designed as simplified analogs of curcumin with maleic diamide tether, were synthesized and bioevaluated. These compounds displayed potent cytotoxicity tow

Method for the Inhibition of Deubiquitinating Activity

A method of treating in a person a cancer tumor refractory to treatment with bortezomib or an agent sharing the apoptosis generating activity of bortezomib or any other anti-cancer drug, comprises administering to the person, in a pharmaceutically acceptable carrier, a pharmacologically effective dose of an agent selected from the group consisting of b-AP15 and other proteasome inhibitor abrogating the deubiquitinating (DUB) activity of the 19S RP DUBs.

A conformational and structure-activity relationship study of cytotoxic 3,5-bis(arylidene)-4-piperidones and related N-acryloyl analogues

A series of 3,5-bis(arylidene)-4-piperidones 1 and related N-acryloyl analogues 2 were prepared as candidate cytotoxic agents with a view to discerning those structural features which contributed to bioactivity. A number of the compounds were markedly cytotoxic toward murine P388 and L1210 leukemic cells and also to human Molt 4/C8 and CEM neoplasms. Approximately 40% of the IC50 values generated were lower than the figures obtained for melphalan. In virtually all cases, the N-acyl compounds were significantly more bioactive than the analogues 1. In general, structure - activity relationships revealed that the cytotoxicity of series 1 was correlated positively with the size of the aryl substituents, while in series 2, a -σ relationship was established. In particular, various angles and interatomic distances were obtained by molecular modeling, and the presence of an acryloyl group on the piperidyl nitrogen atom in series 2 affected the relative locations of the two aryl rings. This observation, along with some differences in distances between various atoms in series 1 and 2, may have contributed to the disparity in cytotoxicity between 1 and 2. The results obtained by X-ray crystallography of representative compounds were mainly in accordance with the observations noted by molecular modeling. Selected compounds interfered with the biosynthesis of DNA, RNA, and protein in murine L1210 cells, while others were shown to cause apoptosis in the human Jurkat leukemic cell line. This study has revealed the potential of these molecules for development as cytotoxic and anticancer agents.