1418013-75-8 Usage
Description
NMS 873 is a potent and specific Valosin-containing protein (VCP) inhibitor, belonging to the AAA (ATPase associated with diverse cellular activities) ATPase family. It plays a significant role in the degradation of misfolded membrane and secretory proteins and is involved in various cellular processes that require unfolding and disassembly of protein complexes. NMS 873 has demonstrated the ability to activate the unfolded protein response, interfere with autophagy, and induce cancer cell death.
Uses
Used in Pharmaceutical Industry:
NMS 873 is used as a therapeutic agent for cancer treatment due to its ability to inhibit the proliferation of cancer cells, particularly HCT116 cancer cells, with an IC50 value of 380 nM. It modulates the VCP/p97 protein, which is overexpressed in many tumor types, and has shown to activate the unfolded protein response, interfere with autophagy, and induce cancer cell death.
Used in Research Applications:
NMS 873 is used as a research tool for studying the role of VCP/p97 in cellular processes and its involvement in various diseases, particularly cancer. It helps researchers understand the molecular mechanisms underlying the regulation of protein homeostasis and the potential therapeutic strategies targeting VCP/p97 in cancer treatment.
Biochem/physiol Actions
NMS-873 is a selective allosteric non–ATP-competitive inhibitor of the AAA ATPase family member valosine containing protein (VCP), also known as p97 (VCP/p97), an integral component of the ubiquitin fusion degradation (UFD) pathway. VCP/p97 plays a role in degradation of misfolded proteins, Golgi membrane reassembly, membrane transport, myofibril assembly, autophagosome maturation, and cell division, and is overexpressed in many tumor types. NMS-873 is the most potent and specific VCP inhibitor described to date. NMS-873 has an IC50 of 30 nM for VCP/p97 compared to IC50 >10 μM against all of the AAA ATPases, HSP90 or the 53 kinases analyzed. NMS-873 inhibited proliferation of HCT116 cancer cell line cells with an IC50 value of 400 nM.
references
[1] magnaghi p, d'alessio r, valsasina b, avanzi n, rizzi s, asa d, gasparri f, cozzi l, cucchi u, orrenius c, polucci p, ballinari d, perrera c, leone a, cervi g, casale e, xiao y, wong c, anderson dj, galvani a, donati d, o'brien t, jackson pk, isacchi a. covalent and allosteric inhibitors of the atpase vcp/p97 induce cancer cell death. nat chem biol. 2013 sep;9(9):548-56. doi: 10.1038/nchembio.1313. epub 2013 jul 28.
Check Digit Verification of cas no
The CAS Registry Mumber 1418013-75-8 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,1,8,0,1 and 3 respectively; the second part has 2 digits, 7 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 1418013-75:
(9*1)+(8*4)+(7*1)+(6*8)+(5*0)+(4*1)+(3*3)+(2*7)+(1*5)=128
128 % 10 = 8
So 1418013-75-8 is a valid CAS Registry Number.
1418013-75-8Relevant articles and documents
Alkylsulfanyl-1,2,4-triazoles, a New Class of allosteric valosine containing protein inhibitors. Synthesis and structure-activity relationships
Polucci, Paolo,Magnaghi, Paola,Angiolini, Mauro,Asa, Daniela,Avanzi, Nilla,Badari, Alessandra,Bertrand, Jay,Casale, Elena,Cauteruccio, Silvia,Cirla, Alessandra,Cozzi, Liviana,Galvani, Arturo,Jackson, Peter K.,Liu, Yichin,Magnuson, Steven,Malgesini, Beatrice,Nuvoloni, Stefano,Orrenius, Christian,Sirtori, Federico Riccardi,Riceputi, Laura,Rizzi, Simona,Trucchi, Beatrice,O'Brien, Tom,Isacchi, Antonella,Donati, Daniele,D'Alessio, Roberto
, p. 437 - 450 (2013/04/10)
Valosine containing protein (VCP), also known as p97, is a member of AAA ATPase family that is involved in several biological processes and plays a central role in the ubiquitin-mediated degradation of misfolded proteins. VCP is an ubiquitously expressed, highly abundant protein and has been found overexpressed in many tumor types, sometimes associated with poor prognosis. In this respect, VCP has recently received a great deal of attention as a potential new target for cancer therapy. In this paper, the discovery and structure-activity relationships of alkylsulfanyl-1,2,4-triazoles, a new class of potent, allosteric VCP inhibitors, are described. Medicinal chemistry manipulation of compound 1, identified via HTS, led to the discovery of potent and selective inhibitors with submicromolar activity in cells and clear mechanism of action at consistent doses. This represents a first step toward a new class of potential anticancer agents.