NMS-E973

製品コードS7282 バッチS728201

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	C₂₂H₂₂N₄O₇
	分子量	454.43	CAS No.	1253584-84-7
Solubility (25°C)*	体外	DMSO	90 mg/mL warmed with 50ºC water bath (198.05 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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-E973 is a potent and selective Hsp90 inhibitor with DC50 of <10 nM for Hsp90 binding, no activiy against a panel of 52 diverse protein kinases.
in vitro	NMS-E973 shows a widespread antiproliferative activity with an average IC50 of 1.6 μM, and induces the degradation of client protein, such as Flt3, B-Raf, AKT, which further blocks tumor-related pathways, such as the Raf/MAPK, PI3K/AKT, and JAK/STAT pathways. ^[1]
in vivo	NMS-E973 (10 mg/kg i.v.) shows a favorable pharmacokinetic profile with selective retention in tumor tissue and ability to cross the BBB. NMS-E973 (60 mg/kg i.v.) shows high antitumor efficacy in all the models tested, including A375 and A2780 xenografts. In addition, NMS-E973 (10 mg/kg i.v.) together with B-Raf inhibitor PLX-4720 at 100 mg/kg produces a synergic anti-tumor effect. ^[1] In a mouse model of human ovarian cancer, NMS-E973 produces the antitumor activity by inhibition of Hsp90. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	Hsp90 binding assays
キナーゼアッセイ	For competition experiments, a protein concentration of 5 nM for Hsp90 and of 200 nM for Trap1 are mixed with 0.5 nmol/L probe (final concentrations). After incubation, the dimethyl sulfoxide (DMSO) compound solution is added to the mixture. The plate is incubated for 18 hours at room temperature and then the fluorescence polarization signal was measured. Data are fitted with the program Dynafit version 3.28.039 or SigmaPlot (SSI) using the mathematical equation for competitive binding of 2 ligands to the receptor.
細胞アッセイ	細胞株	140 human tumor cell lines of various tissue origins and molecular background.
	濃度	~10 μM
	反応時間
	実験の流れ	Exponentially growing cells are seeded in complete medium in a 384-well plate format. 24 hours after seeding, cells are treated with compounds dissolved in 0.1% DMSO, at different concentrations. The cells are incubated at 37°C and 5% CO₂ and at the end of treatment time, the plates are processed using Cell Titer-Glo assay following the manufacturer's instruction. CellTiter-Glo is a homogenous method based on the quantification of the ATP present, an indicator of metabolically active cells. Briefly, 25 μL reagent solution is added to each well and after 5 minutes of shaking the microplates, the luminescent signal is read by Envision luminometer. Inhibitory activity is evaluated comparing treated versus control data using sigmoidal equation on Assay Explorer program.
動物実験	動物モデル	Mice bearing A375 xenografts, A2780 xenografts, MOLM-13 xenografts or RKO xenografts.
	投薬量	~60 mg/kg
	投与方法	i.v.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Onco Targets Ther, 2018, 11:1583-1593]

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：

deepOrganoid: A brightfield cell viability model for screening matrix-embedded organoids [ SLAS Discov, 2022, 27(3):175-184]	PubMed: 35314378
HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance [ J Exp Clin Cancer Res, 2021, 40(1):170]	PubMed: 33990203
Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation [ Mol Cancer, 2020, 19(1):112]	PubMed: 32600329
Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells. [ Immunity, 2020, 52(2):328-341]	PubMed: 32049050
Hsp90 inhibitor HSP990 in very low dose upregulates EAAT2 and exerts potent antiepileptic activity [ Theranostics, 2020, 10(18):8415-8429]	PubMed: 32724478
Evaluation of [11C]NMS-E973 as a PET tracer for in vivo visualisation of HSP90 [Koen Vermeulen, et al. Theranostics, 2019, 9(2):554-572]
Evaluation of [11C]NMS-E973 as a PET tracer for in vivo visualisation of HSP90. [ Theranostics, 2019, 9(2):554-572]	PubMed: 30809293
Hsp90 inhibitor NMS-E973 exerts the anticancer effect against glioblastoma via induction of PUMA-mediated apoptosis. [ Onco Targets Ther, 2018, 11:1583-1593]	PubMed: 29593424
Combined inhibition of Hsp90 and heme oxygenase-1 induces apoptosis and endoplasmic reticulum stress in melanoma [Barbagallo I, et al. Acta Histochem, 2015, 117(8):705-11]	PubMed: 26493719

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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