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）

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.
Clear solution	5%DMSO 1 Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.500mg/ml (1.59mM)	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 (BAY 85-3934) induces the transcription of hypoxia-sensitive genes in HeLa, A549, and Hep3B cells. ^[1]
in vivo	Molidustat (BAY 85-3934) (1.5 mg/kg, p.o.) induces dose-dependent production of EPO and erythropoiesis in healthy Wistar rats and cynomolgus monkeys. In rats with induced renal anemiabe, this compound (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 Molidustat (BAY 85-3934) 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 for this compound are determined after curve fitting using GraphPad Prism software applying the four-parameter logistic equation to the data sets.
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 this compound for 24 h.
動物実験	動物モデル	Rats with induced renal anemia
	投薬量	5 mg/kg
	投与方法	p.o.

参考

https://pubmed.ncbi.nlm.nih.gov/25392999/
https://pubmed.ncbi.nlm.nih.gov/33852916/

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：

The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia [ Nat Cancer, 2024, 10.1038/s43018-024-00761-w]	PubMed: 38637657
Focused Screening Identifies Different Sensitivities of Human TET Oxygenases to the Oncometabolite 2-Hydroxyglutarate [ J Med Chem, 2024, 67(6):4525-4540]	PubMed: 38294854
Pharmacologic HIF stabilization activates costimulatory receptor expression to increase antitumor efficacy of adoptive T cell therapy [ Sci Adv, 2024, 10(35):eadq2366]	PubMed: 39196939
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
Stabilisation of HIF signalling extends epicardial activation and neonatal heart regeneration [ Research Square, 2023, PPR608501 ]	PubMed: None
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

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。