NMS-873

製品コードS7285 バッチS728501

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₇H₂₈N₄O₃S₂

分子量

520.67

CAS No.

1418013-75-8

Solubility (25°C)*

体外

DMSO

100 mg/mL (192.06 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	NMS-873 is an allosteric and specific p97 inhibitor with IC50 of 30 nM that demonstrates potent selectivity for VCP/p97 compared to a panel of other AAA ATPases, Hsp90, and 53 additional analyzed kinases (IC50s >10 μM).
in vitro	NMS-873 reduces p97 sensitivity to trypsin digestion, preventing degradation of the linker-D2 domain. This compound, as a p97 inhibitor, produces antiproliferative activity in a variety of hematological and solid tumor lines. The mechanism study indicates that this chemical activates the unfolded protein response, interfers with autophagy and thus induces cancer cell death. ^[1]
特徴	The most potent and specific p97 inhibitor described to date.

プロトコル(参考用のみ)

キナーゼアッセイ	Biochemical assay development and HTS
キナーゼアッセイ	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 assay. 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 plates in a reaction buffer with 50 mM Hepes, pH 7.5, 0.2 mg/mL BSA, 10 mM MgCl₂ and 2 mM DTT. Experimental data are fitted with a cooperative equation obtaining a Ks* of about 60 μM and a Hill coefficient (n) of 2.0 ± 0.1. The HTS campaign is performed against a 1-million-compound library using a miniaturized assay in 1,536-well format and a more sensitive ADP detection system, Transcreener ADP FP. A 20-min preincubation of 10 nM VCP and 10 μM inhibitor is performed, after which 10 μM ATP is added to the reaction, which is allowed to proceed for 90 min before quenching. The average Z′ of the screening is 0.58, and the hit rate using 3× s.d. (38% inhibition) as cutoff is 1.7%. Primary hits with >60% inhibition at 10-μM concentration are pruned using physicochemical and structural filters to leave 7,516 compounds. At the end, reconfirmation is performed in duplicate on 3,988 primary hits, and 500 compounds are selected for a dose-response evaluation using the previously described NADH-modified coupled assay. The potency of the most interesting HTS hits is measured against both wild-type VCP and the C522T mutant. ATP concentrations that yielded the half-maximal velocity (Ks*) for each enzyme, corresponding to 60 μM and 130 μM for the wild type and C522T mutant, respectively, are used in the assay. To explore the dependency of reversible inhibitors from substrate concentration, their potency is evaluated also at saturating ATP concentration (1 mM) and compared to the potency of a standard ATP competitive inhibitor (AMP-PNP).
細胞アッセイ	細胞株	A variety of hematological and solid tumor lines
	濃度	~10 μM
	反応時間	72 hours
	実験の流れ	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 as a measure of cell viability. IC50 values are calculated using the percentage of growth of treated cells versus the untreated control.

参考

https://pubmed.ncbi.nlm.nih.gov/23892893/

カスタマーフィードバック

: , , Toxicol Appl Pharmacol, 2016, 305:267-73.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Targeting site-specific N-glycosylated B7H3 induces potent antitumor immunity [ Nat Commun, 2025, 16(1):3546]	PubMed: 40229277
Curcumin Induces Homologous Recombination Deficiency by BRCA2 Degradation in Breast Cancer and Normal Cells [ Cancers (Basel), 2025, 17(13)2109]	PubMed: 40647408
The Fanconi anemia pathway induces chromothripsis and ecDNA-driven cancer drug resistance [ Cell, 2024, 187(21):6055-6070.e22]	PubMed: 39181133
Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function [ Cell, 2024, 187(21):5967-5980.e17]	PubMed: 39276772
Transcription-coupled DNA-protein crosslink repair by CSB and CRL4CSA-mediated degradation [ Nat Cell Biol, 2024, 10.1038/s41556-024-01394-y]	PubMed: 38600236
Sugar-mediated non-canonical ubiquitination impairs Nrf1/NFE2L1 activation [ Mol Cell, 2024, 84(16):3115-3127.e11]	PubMed: 39116872
Reactive oxygen species control protein degradation at the mitochondrial import gate [ Mol Cell, 2024, 84(23):4612-4628.e13]	PubMed: 39642856
Differential processing of RNA polymerase II at DNA damage correlates with transcription-coupled repair syndrome severity [ Nucleic Acids Res, 2024, gkae618]	PubMed: 39021334
The protein segregase VCP/p97 promotes host antifungal defense via regulation of SYK activation [ PLoS Pathog, 2024, 20(10):e1012674]	PubMed: 39471181
Inhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746 [ iScience, 2024, 27(11):110961]	PubMed: 39759071

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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