(S)-crizotinib

製品コードS7505 バッチS750502

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	C₂₁H₂₂Cl₂FN₅O
	分子量	450.34	CAS No.	1374356-45-2
Solubility (25°C)*	体外	DMSO	42 mg/mL warmed with 50ºC water bath (93.26 mM)
		Ethanol	22 mg/mL (48.85 mM)
		Water	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	(S)-crizotinib, the (S)-enantiomer of crizotinib, is a potent MTH1 (NUDT1) inhibitor with IC50 of 72 nM in a cell-free assay.
in vitro	(S)-crizotinib disrupts nucleotide pool homeostasis via MTH1 inhibition, induces an increase in DNA single-strand breaks, and activates DNA repair in human colon carcinoma cells. ^[1]
in vivo	(S)-Crizotinib (50 mg/kg, orally, daily) impairs tumor growth in an SW480 colon carcinoma xenograft model. ^[1]
特徴	MTH1 (NUDT1)- selective inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ	MTH1 catalytic assay
キナーゼアッセイ	Half-maximal inhibitory concentrations (IC50) are determined using a luminescence-based assay with some minor modifications. Briefly, serial dilutions of compounds are dissolved in assay buffer (100 mM Tris-acetate pH 7.5, 40 mM NaCl and 10 mM Mg(OAc)2 containing 0.005% Tween-20 and 2 mM dithiothreitol (DTT). Upon addition of MTH1 recombinant protein (final concentration 2 nM), plates are incubated on a plate shaker for 15 min at room temperature. After addition of the substrate dGTP (final concentration 100 µM), 8-oxo-dGTP (final concentration 13.2 µM), or 2-OH-dATP (final concentration 8.3 µM) the generation of pyrophosphate (PPi) as a result of nucleotide triphosphate hydrolysis by MTH1 is monitored over a time course of 15 min using the PPi Light Inorganic Pyrophosphate Assay kit. IC50 values are determined by fitting a dose-response curve to the data points using nonlinear regression analysis using the GraphPad Prism software.
細胞アッセイ	細胞株	PANC1 and SW480 cells
	濃度	~5 礛
	反応時間	7-10 days
	実験の流れ	One day before treatment, cells are seeded per well in six-well plates and incubated for 24 h. The next day DMSO (equal to highest amount of compound dilution, maximum 0.2%) or compounds in increasing concentrations were added and cells incubated at 37 °C, 5% CO₂, for 7-10 days. After washing with PBS, cells are fixed with ice-cold methanol, stained with crystal violet solution (0.5% in 25% methanol) and left to dry overnight. For quantification of results, ultraviolet absorbance of crystal violet is determined at 595 nm following solubilisation by 70% ethanol. Data are analysed using nonlinear regression analysis using the GraphPad Prism software.
動物実験	動物モデル	SW480 colon carcinoma xenograft mouse model.
	投薬量	1% DMSO, 10% ethanol, 10% Cremophor, 10% Tween 80, 69% PBS
	投与方法	p.o.

参考

[1] Huber KV, et al. Nature. 2014 , 508(7495), 222-227.

カスタマーフィードバック

: Data from [Data independently produced by , , Cancer Letters, 2014, 35(2):215-221.]

: Data from [Data independently produced by , , Onco Targets Ther, 2015, 8: 3649-3664.]

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：

Generation of Human Blood Vessel and Vascularized Cerebral Organoids [ Bio Protoc, 2023, 10.21769/BioProtoc.4870]	PubMed: 37969757
Oxidized DNA Precursors Cleanup by NUDT1 Contributes to Vascular Remodeling in PAH [ Am J Respir Crit Care Med, 2020, 10.1164/rccm.202003-0627OC]	PubMed: 33021405
Low Replicative Fitness of Neuraminidase Inhibitor-Resistant H7N9 Avian Influenza a Virus With R292K Substitution in Neuraminidase in Cynomolgus Macaques Compared With I222T Substitution [ Antiviral Res, 2020, 178:104790]	PubMed: 32272175
Application of a Biphasic Mathematical Model of Cancer Cell Drug Response for Formulating Potent and Synergistic Targeted Drug Combinations to Triple Negative Breast Cancer Cells. [ Cancers (Basel), 2020, 27;12(5)pii: E1087]	PubMed: 32349331
Biphasic Mathematical Model of Cell-Drug Interaction That Separates Target-Specific and Off-Target Inhibition and Suggests Potent Targeted Drug Combinations for Multi-Driver Colorectal Cancer Cells. [ Cancers (Basel), 2020, 13;12(2) pii: E436]	PubMed: 32069833
Efficient Blockade of Locally Reciprocated Tumor-Macrophage Signaling Using a TAM-avid Nanotherapy [ Sci Adv, 2020, 22;6(21):eaaz8521]	PubMed: 32494745
VISAGE Reveals a Targetable Mitotic Spindle Vulnerability in Cancer Cells. [ Cell Syst, 2019, 9(1):74-92.e8]	PubMed: 31302152
TLR7/8-agonist-loaded Nanoparticles Promote the Polarization of Tumour-Associated Macrophages to Enhance Cancer Immunotherapy [ Nat Biomed Eng, 2018, 2(8):578-588]	PubMed: 31015631
(S)-crizotinib reduces gastric cancer growth through oxidative DNA damage and triggers pro-survival akt signal. [ Cell Death Dis, 2018, 9(6):660]	PubMed: 29855474
(S)-crizotinib induces apoptosis in human non-small cell lung cancer cells by activating ROS independent of MTH1. [ J Exp Clin Cancer Res, 2017, 36(1):120]	PubMed: 28882182

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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