NMS-873

Modify Date: 2024-01-02 17:39:11

NMS-873 Structure
NMS-873 structure
Common Name NMS-873
CAS Number 1418013-75-8 Molecular Weight 520.666
Density 1.3±0.1 g/cm3 Boiling Point 769.3±70.0 °C at 760 mmHg
Molecular Formula C27H28N4O3S2 Melting Point N/A
MSDS Chinese USA Flash Point 419.0±35.7 °C
Symbol GHS07
GHS07
Signal Word Warning

 Use of NMS-873


NMS-873 is a potent, selective allosteric VCP/p97 inhibitor with IC50 value of 30 nM.

 Names

Name 3-[3-(Cyclopentylsulfanyl)-5-({[2-methyl-4'-(methylsulfonyl)-4-bi phenylyl]oxy}methyl)-4H-1,2,4-triazol-4-yl]pyridine
Synonym More Synonyms

 NMS-873 Biological Activity

Description NMS-873 is a potent, selective allosteric VCP/p97 inhibitor with IC50 value of 30 nM.
Related Catalog
Target

IC50: 30 nM[1]

In Vitro NMS-873 has antiproliferative effect on a panel of tumor cell lines with IC50 values in the range of 0.08 μM to 2 μM. For HCT116 and HeLa cells, the IC50 values are 0.4 μM and 0.7 μM, respectively. NMS-873 reduces VCP sensitivity to trypsin digestion, preventing degradation of the linker-D2 domain. NMS-873 induces clear, dose-dependent accumulation of poly-Ub proteins and stabilization of cyclin E and Mcl-1 at doses consistent with its antiproliferative IC50 value[1].
Kinase Assay The ATPase activity and the kinetic parameters of recombinant wild-type VCP and its mutants are evaluated by monitoring ADP formation in the reaction, using a modified NADH-coupled assay46. As ADP and NADH are ATP-competitive inhibitors of VCP ATPase activity, the standard protocol for the NADH-coupled assay is modified into a two-step procedure. In the first part, an ATP-regenerating system (40 U/mL pyruvate kinase and 3 mM phosphoenolpyruvate) recycles the ADP produced by VCP activity, keeps the substrate concentration constant (thus preventing product inhibition) and accumulates a stoichiometric amount of pyruvate. In the second part, the VCP enzymatic reaction is quenched with 30 mM EDTA and 250 μM NADH and stoichiometrically oxidized by 40 U/mL lactic dehydrogenase to reduce accumulated pyruvate. The decrease of NADH concentration is measured at 340 nm using a Tecan Safire 2 reader plate. The assay is performed in 96- or 384-well UV platesin a reaction buffer with 50 mM Hepes, pH 7.5, 0.2 mg/mL BSA, 10 mM MgCl2 and 2 mM DTT.
Cell Assay Cells are seeded at 1,600 cells per well in 384-well white clear-bottom plates. Twenty-four hours after seeding, cells are treated with the compounds (eight dilution points, in duplicate, for each compound) and incubated for an additional 72 h at 37°C under a 5% CO2 atmosphere. Cells are then lysed, and the ATP content in each well is determined using a thermostable firefly luciferase-based assay from Promega as a measure of cell viability. IC50 values are calculated using the percentage of growth of treated cells versus the untreated control.
References

[1]. Paola Magnaghi, et al. Covalent and allosteric inhibitors of the ATPATP ase VCP/p97 induce cancer cell death. Nat Chem Biol. 2013 Jul 28. doi: 10.1038/nchembio.1313.

 Chemical & Physical Properties

Density 1.3±0.1 g/cm3
Boiling Point 769.3±70.0 °C at 760 mmHg
Molecular Formula C27H28N4O3S2
Molecular Weight 520.666
Flash Point 419.0±35.7 °C
Exact Mass 520.160278
PSA 120.65000
LogP 4.77
Appearance of Characters white to beige
Vapour Pressure 0.0±2.6 mmHg at 25°C
Index of Refraction 1.675
Storage condition 2-8°C
Water Solubility DMSO: soluble25mg/mL, clear

 Safety Information

Symbol GHS07
GHS07
Signal Word Warning
Hazard Statements H302
Hazard Codes Xn
Risk Phrases 22
RIDADR NONH for all modes of transport

 Synthetic Route

~39%

NMS-873 Structure

NMS-873

CAS#:1418013-75-8

Literature: 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 Journal of Medicinal Chemistry, 2013 , vol. 56, # 2 p. 437 - 450

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NMS-873 Structure

NMS-873

CAS#:1418013-75-8

Literature: 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 Journal of Medicinal Chemistry, 2013 , vol. 56, # 2 p. 437 - 450

~%

NMS-873 Structure

NMS-873

CAS#:1418013-75-8

Literature: 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 Journal of Medicinal Chemistry, 2013 , vol. 56, # 2 p. 437 - 450

 Synonyms

Pyridine, 3-[3-(cyclopentylthio)-5-[[[2-methyl-4'-(methylsulfonyl)[1,1'-biphenyl]-4-yl]oxy]methyl]-4H-1,2,4-triazol-4-yl]-
3-[3-(Cyclopentylsulfanyl)-5-({[2-methyl-4'-(methylsulfonyl)-4-biphenylyl]oxy}methyl)-4H-1,2,4-triazol-4-yl]pyridine
NMS-873
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