AZD7545

製品コードS7517 バッチS751701

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

C₁₉H₁₈ClF₃N₂O₅S

分子量

478.87

CAS No.

252017-04-2

Solubility (25°C)*

体外

DMSO

95 mg/mL (198.38 mM)

Ethanol

95 mg/mL (198.38 mM)

Water

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 40%PEG300 2 5%Tween80 3 50%ddH2O 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。	4.750mg/ml (9.92mM)	Taking the 1 mL working solution as an example, add 50 μL of 95 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% 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。	0.790mg/ml (1.65mM)	Taking the 1 mL working solution as an example, add 50 μL of 15.8 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	AZD7545は、PDHKの強力な阻害剤であり、PDHK1に対しては36.8 nM、PDHK2に対しては6.4 nMのIC50値を示します。より高濃度（>10 nM）ではPDHK4を阻害せず、AZD7545はPDHK4活性を刺激します。
in vitro	In the presence of recombinant human PDHK2, AZD7545 increases PDH activity with EC50 of 5.2 nM. In primary rat hepatocytes, this compound increases PDH activity with EC50 of 105 nM. It inhibits PDHK activity by disrupting the interactions between PDHK2 and the inner lipoyl-bearing domains (L2) of the dihydrolipoyl transacetylase component (E2) of PDC.
in vivo	In Wistar rats, AZD7545 increases the percentage of active PDH in the liver and skeletal muscle. In obese, insulin-resistant, Zucker rats, this compound eliminates the postprandial elevation in blood glucose.

プロトコル(参考用のみ)

キナーゼアッセイ	Inhibition of PDHK isoenzyme assay
キナーゼアッセイ	The incorporation of [³³P]ATP into the E1 subunit of PDH is measured at 30°C in Mops-K+ buffer in the presence of 100 mM ATP and E2 subunit. Recombinant human proteins are used throughout. Compounds J, K and L are from the same chemical series as this compound. IC50 values are means±.E.M. with the number of observations given in parentheses.
動物実験	動物モデル	The obese (fa/fa) Zucker rats
	投薬量	~30 mg/kg twice daily
	投与方法	p.o.

参考

https://pubmed.ncbi.nlm.nih.gov/14641019/
https://pubmed.ncbi.nlm.nih.gov/14641018/
https://pubmed.ncbi.nlm.nih.gov/17602666/

カスタマーフィードバック

: Data from [Data independently produced by , , Mol Cancer, 2017, 16(1):102]

: Data from [Data independently produced by , , J Pharm Pharmacol, 2017, 69(1):43-51]

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：

Hypoxia-induced reprogramming of glucose-dependent metabolic pathways maintains the stemness of human bone marrow-derived endothelial progenitor cells [ Sci Rep, 2023, 13(1):8776]	PubMed: 37258701
Systemic Metabolic and Mitochondrial Defects in Rett Syndrome Models [ bioRxiv, 2023, 10.1101/2023.04.03.535431]	PubMed: None
Systemic Metabolic and Mitochondrial Defects in Rett Syndrome Models [ bioRxiv, 2023, 2023.04.03.535431]	PubMed: 37066332
Inhibition of aberrant Hif1α activation delays intervertebral disc degeneration in adult mice [ Bone Res, 2022, 10(1):2]	PubMed: 34983922
The Combined Use of Orf Virus and PAK4 Inhibitor Exerts Anti-tumor Effect in Breast Cancer [ Int J Mol Sci, 2022, 23(7)3745]	PubMed: 35409102
Increased demand for NAD+ relative to ATP drives aerobic glycolysis [ Mol Cell, 2021, 81(4):691-707.e6]	PubMed: 33382985
mTOR-mediated cancer drug resistance suppresses autophagy and generates a druggable metabolic vulnerability [ Nat Commun, 2020, 11(1):4684]	PubMed: 32943635
Increased demand for NAD+ relative to ATP drives aerobic glycolysis [ Mol Cell, 2020, S1097-2765(20)30904-7]	PubMed: 33382985
ROS production induced by BRAF inhibitor treatment rewires metabolic processes affecting cell growth of melanoma cells. [Cesi G, et al. Mol Cancer, 2017, 16(1):102]	PubMed: 28595656
Dichloroacetate induces regulatory T-cell differentiation and suppresses Th17-cell differentiation by pyruvate dehydrogenase kinase-independent mechanism. [Makita N, et al. J Pharm Pharmacol, 2017, 69(1):43-51]	PubMed: 27757958

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。