Molidustat (BAY 85-3934)

製品コードS8138 バッチS813803

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

C₁₃H₁₄N₈O₂

分子量

314.30

CAS No.

1154028-82-6

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

10 mg/mL (31.81 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）

Clear solution

5%DMSO 1 Corn oil

0.5mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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	Molidustat (BAY 85-3934) is a potent hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor with IC50 of 480 nM, 280 nM, and 450 nM for PHD1, PHD2, and PHD, respectively. Phase 2.
in vitro	In vitro, Molidustat induces the transcription of hypoxia-sensitive genes in HeLa, A549, and Hep3B cells. ^[1]
in vivo	In healthy Wistar rats and cynomolgus monkeys, Molidustat (1.5 mg/kg, p.o.) induces dose-dependent production of EPO and erythropoiesis. In rats with gentamicin-induced renal anemiabe, Molidustat (5 mg/kg, p.o.) is also effective in raising hematocrit levels while stimulating endogenous EPO production without hypertensive effects. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Prolyl hydroxylase assay
キナーゼアッセイ	Biotinylated HIF-1α 556–574 (biotinyl-DLDLEMLAPYIPMDDDFQL) is bound to white 96-well NeutrAvidin high binding capacity plates, which are pre-blocked with Blocker Casein and subsequently blocked with 1 mM biotin. The immobilized peptide substrate is incubated with the appropriate amount of HIF-PH in buffer containing 20 mM Tris (pH 7.5), 5 mM KCl, 1.5 mM MgCl₂, 20 µM 2-oxoglutarate, 10 µM FeSO₄, 2 mM ascorbate, 4% protease inhibitors without EDTA in a final volume of 100 µl, with or without test compound added at appropriate concentrations. The reaction time is 60 min. To stop the reaction, plates are washed three times with wash buffer. Hydroxylated biotinyl-HIF-1α 556–574 is incubated with Eu-VBC in 100 µl binding buffer (50 mM Tris [pH 7.5], 120 mM NaCl) for 60 min at room temperature. After washing six times with DELFIA wash buffer and adding 100 µl enhancer solution, the amount of bound VBC is determined by measuring time-resolved fluorescence with a Tecan infinite M200 plate reader. Measurements are taken in triplicate or more, and results are expressed as means ± SEM. IC50 values are determined after curve fitting using GraphPad Prism software applying the four-parameter logistic equation to the data sets. When adjustment of the concentration of free Fe2+ is necessary, the reaction buffer is supplemented with appropriate amounts of ammonium iron(II) sulfate ((NH4)2Fe(SO4)2.6H2O).
細胞アッセイ	細胞株	Calu-3 cells
	濃度	6 μM
	反応時間	24 h
	実験の流れ	Cells were treated with various concentrations of drug for 24 h.
動物実験	動物モデル	Rats with gentamicin-induced renal anemia
	投薬量	5 mg/kg
	投与方法	p.o.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Theranostics, 2017, 7(13): 3293-3305]

: Data from [Data independently produced by , , Theranostics, 2017, 7(13):3293-3305]

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：

Focused Screening Identifies Different Sensitivities of Human TET Oxygenases to the Oncometabolite 2-Hydroxyglutarate [ J Med Chem, 2024, 67(6):4525-4540]	PubMed: 38294854
Osteocyte Egln1/Phd2 links oxygen sensing and biomineralization via FGF23 [ Bone Res, 2023, 11(1):7]	PubMed: 36650133
Drugs That Mimic Hypoxia Selectively Target EBV-Positive Gastric Cancer Cells [ Cancers (Basel), 2023, 15(6)1846]	PubMed: 36980731
Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells [ Cell Rep, 2021, 35(3):109020]	PubMed: 33852916
Stabilization of Hypoxia-Inducible Factor Promotes Antimicrobial Activity of Human Macrophages Against Mycobacterium tuberculosis [ Front Immunol, 2021, 12:678354]	PubMed: 34149713
The HIF-PHI BAY 85-3934 (Molidustat) Improves Anemia and Is Associated With Reduced Levels of Circulating FGF23 in a CKD Mouse Model [ J Bone Miner Res, 2021, 10.1002/jbmr.4272]	PubMed: 33592127
Sodium-glucose Cotransporter 2 Inhibition Suppresses HIF-1α-mediated Metabolic Switch From Lipid Oxidation to Glycolysis in Kidney Tubule Cells of Diabetic Mice [ Cell Death Dis, 2020, 22;11(5):390]	PubMed: 32444604
HIF hydroxylase inhibitors decrease cellular oxygen consumption depending on their selectivity. [ FASEB J, 2020, 34(2):2344-2358]	PubMed: 31908020
Prolyl-hydroxylase inhibitors reconstitute tumor blood vessels in mice. [ J Pharmacol Sci, 2020, 10.1016]	PubMed: 32199747
Long Non-Coding RNA CASC9 And HIF-1α Form A Positive Feedback Loop To Facilitate Cell Proliferation And Metastasis In Lung Cancer. [ Onco Targets Ther, 2019, 12:9017-9027]	PubMed: 31802910

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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