Zosuquidar 3HCl

製品コードS1481 バッチS148102

化学情報

	Synonyms	LY335979 3HCl, RS 33295-198 3HCl, D06387 3HCl	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₃₂H₃₁F₂N₃O₂.3HCl
	分子量	636.99	CAS No.	167465-36-3
Solubility (25°C)*	体外	DMSO	127 mg/mL (199.37 mM)
		Water	23 mg/mL (36.1 mM)
		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	Zosuquidar 3HCl is a potent modulator of P-glycoprotein-mediated multi-drug resistance with K_i of 60 nM in a cell-free assay. Phase 3.
in vitro	LY335979 competitively inhibits equilibrium binding of [³H]vinblastine to Pgp by blocking [³H]azidopine photoaffinity labeling of the Pgp in CEM/VLB₁₀₀ plasma membranes. ^[1] LY335979 alone shows the cytotoxicity to drug-sensitive and MDR cell lines with IC50 ranging from 6 μM-16 μM and produces its ability to completely reverse the resistance of the oncolytics (vinblastine, doxorubicin, or etoposide) to the MDR cell lines P388/ADR, MCF7/ADR, 2780AD, or UCLA-P3.003VLB at concentration of 0.1 and 0.5 μM. ^[1] LY335979 significantly restores drug sensitivity in P-gp-expressing leukemia cell lines including K562/HHT40, K562/HHT90, K562/DOX and HL60/DNR, and enhances the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) in primary AML blasts with active P-gp. ^[2] A latest paper indicates that LY335979 completely inhibits apically directed transport of (Z)-endoxifen in the ABCB1-transduced cells. ^[3]
in vivo

プロトコル(参考用のみ)

キナーゼアッセイ	ATPase Assay
キナーゼアッセイ	P-Glycoprotein ATPase activity is measured by the liberation of inorganic phosphate from ATP. The assay is measured in a 96-well plate for 90 min at 37 °C. Membranes (8 μg-10 μg protein) are incubated in a total volume of 100 μL of buffer A containing 5 mM sodium azide, 1 mM ouabain, 1 mM EGTA, 3 mM ATP, an ATP regenerating system composed of 5 mM phosphoenolpyruvate, and 3.6 units/mL pyruvate kinase in the presence and absence of 1 mM sodium vanadate. Pgp-ATPase activity is defined as the vanadate-sensitive portion of the total ATPase activity. Plates are read 3 minutes after the addition of the detection solution. The absorbance is measured at 690 nm by a microtiter dish reader. A phosphate standard curve is used to calculate the μmol of phosphate formed. Samples are measured in triplicate.
細胞アッセイ	細胞株	CEM/VLB₁₀₀, P388/ADR, MCF7/ADR, 2780AD, and UCLA-P3.OO3VLB cells
	濃度	0.05 μM to 5 μM
	反応時間	72 hours
	実験の流れ	Cell viability is determined using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method. Cells are harvested during logarithmic growth phase, and seeded in 96-well plates. The cells are then cultured for 72 hours in the presence of oncolytics with or without modulators. MCF-7 and MCF-7/ADR cells are incubated 24 hours before the addition of the drug with and without the LY335979. LY335979 is prepared as 2 mM DMSO stocks and added to wells to give final concentrations ranging from 0.05 to 5 μM. After 72 hours, 20 μL of freshly prepared 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (5 mg/mL in Dulbecco's PBS) is added to each well and incubated for 4 hours in a 37 °C incubator containing 5% CO₂. Cells are pelleted in a Sorvall RT6000B centrifuge, 70 μL of medium is carefully removed from each well, and 100 μL of 2-propanol/0.04 N HC1 is added. Cells are resuspended 5-10 times with a Multipipettor or until no particulate matter is visible. Plates are immediately read on a Titertek Multiskan MCC/340 microplate reader Flow Laboratories with a test wavelength of 570 nm and a reference wavelength of 630 nm. Controls are measured in quadruplicate and modulators are measured in duplicate. Cytotoxicity analyses are also performed using the CeliTiter 96 AQueous assay kit.
動物実験	動物モデル	P388 or P388/ADR cells are implanted by i.p. injection into female BDF₁ mice.
	投薬量	≤30 mg/kg
	投与方法	Administered via i.p. and i.v.

参考

カスタマーフィードバック

: Data from [Data independently produced by J Lipid Res, 2014, 10.1194/jlr.M052761]

: Data from [Data independently produced by Aquat Toxicol, 2014, 156C, 135-147]

: Data from [Pharmacol Res, 2013, 67(1), 79-83]

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：

Functional Blood-Brain Barrier Model with Tight Connected Minitissue by Liquid Substrates Culture [ Adv Healthc Mater, 2022, e2201984]	PubMed: 36394091
Overcoming Resistance to Anti–Nectin-4 Antibody-Drug Conjugate [ Mol Cancer Ther, 2022, 21 (7): 1227–1235.]	PubMed: None
Overcoming Resistance to Anti-nectin-4 Antibody-Drug Conjugate [ Mol Cancer Ther, 2022, molcanther.0013.2022]	PubMed: 35534238
Brain endothelial cells metabolize glutamate via glutamate dehydrogenase to replenish TCA-intermediates and produce ATP under hypoglycemic conditions [ J Neurochem, 2021, 157(6):1861-1875]	PubMed: 33025588
Heat Shock Protein Inhibitor 17-Allyamino-17-Demethoxygeldanamycin, a Potent Inductor of Apoptosis in Human Glioma Tumor Cell Lines, Is a Weak Substrate for ABCB1 and ABCG2 Transporters [ Pharmaceuticals (Basel), 2021, 14(2)107]	PubMed: 33573093
The blood-brain barrier studied in vitro across species [ PLoS One, 2021, 16(3):e0236770]	PubMed: 33711041
Characterization of human pregnane X receptor activators identified from a screening of the Tox21 compound library [ Biochem Pharmacol, 2020, S0006-2952(20)30604-3]	PubMed: 33333074
Testing of the Survivin Suppressant YM155 in a Large Panel of Drug-Resistant Neuroblastoma Cell Lines. [ Cancers (Basel), 2020, 2;12(3) pii: E577]	PubMed: 32131402
Pranlukast Antagonizes CD49f and Reduces Stemness in Triple-Negative Breast Cancer Cells [ Drug Des Devel Ther, 2020, 12;14:1799-1811]	PubMed: 32494122
MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes [ Sci Rep, 2020, 10(1):22124]	PubMed: 33335181

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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