1009817-63-3 Usage
Description
b-AP15, also known as (3E,5E)-1-Acryloyl-3,5-bis(4-nitrobenzylidene)piperidin-4-one, is a compound that inhibits the deubiquitinating activity of the 19S regulatory particle by targeting ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14). This results in the accumulation of polyubiquitin in cells and has been shown to induce tumor cell apoptosis and tumor progression in various solid tumor models in vivo. b-AP15 is a promising candidate for cytotoxic activity against malignant cells.
Uses
Used in Anticancer Applications:
b-AP15 is used as a cytotoxic agent for malignant cells, particularly in the treatment of various solid tumors. It works by inhibiting the deubiquitinating activity of the 19S regulatory particle, leading to the accumulation of polyubiquitin in cells and inducing tumor cell apoptosis. This makes b-AP15 a potential therapeutic option for cancer patients.
Used in Drug Development:
b-AP15 is used as a lead compound in the development of new drugs targeting the ubiquitin-proteasome system, which plays a crucial role in various cellular processes, including cell cycle regulation, signal transduction, and protein homeostasis. By inhibiting specific enzymes involved in this system, b-AP15 may help in the development of novel therapeutic strategies for cancer treatment.
Used in Research:
b-AP15 is used as a research tool to study the role of the ubiquitin-proteasome system in cancer cell biology. Its ability to inhibit the deubiquitinating activity of the 19S regulatory particle and induce tumor cell apoptosis makes it a valuable compound for investigating the molecular mechanisms underlying cancer development and progression. This knowledge can be applied to the development of targeted therapies and personalized treatment strategies for cancer patients.
in vitro
nsc 687852 blocked deubiquitylating activity of usp14 and uchl5 selectively without inhibiting proteasome activity. nsc 687852 decreased viability in multiple myeloma (mm) cell lines and patient mm cells, inhibited mm cell proliferation even in the presence of bone marrow stroma cells, and overcomed bortezomib resistance. anti-mm activity of nsc 687852 was associated with growth arrest through downregulating cdc2, cdc25c, and cyclin b1, as well as induction of caspase-dependent apoptosis and activation of unfolded protein response [1].
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)
in vivo
in vivo studies using distinct human mm xenograft models showed that nsc 687852 was well tolerated, inhibited tumor growth, and prolonged mouse survival. combination of nsc 687852 with suberoylanilide hydroxamic acid, lenalidomide, or dexamethasone was found to induce synergistic anti-mm activity [1].
References
1) D’Arcy et al. (2011), Inhibition of proteasome deubiquitinating activity as a new cancer therapy; Nature Medicine, 17 1636
Check Digit Verification of cas no
The CAS Registry Mumber 1009817-63-3 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,0,9,8,1 and 7 respectively; the second part has 2 digits, 6 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 1009817-63:
(9*1)+(8*0)+(7*0)+(6*9)+(5*8)+(4*1)+(3*7)+(2*6)+(1*3)=143
143 % 10 = 3
So 1009817-63-3 is a valid CAS Registry Number.
