TEPP-46 (ML265)

製品コードS7302 バッチS730201

化学情報

	Synonyms	CID-44246499, NCGC00186528	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₇H₁₆N₄O₂S₂
	分子量	372.46	CAS No.	1221186-53-3
Solubility (25°C)*	体外	DMSO	74 mg/mL (198.67 mM)
		Water	Insoluble
		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	TEPP-46 (ML265, CID-44246499, NCGC00186528) is a potent activator of PKM2 in both biochemical (AC50 = 92 nM) and cell-based assays with high selectivity over PKM1, PKR and PKL.
in vitro	ML265 potently activates PKM2 in vitro with an AC50 = 92 nM and shows a high degree of selectivity over the other 3 pyruvate kinase isoforms. ML265 binds at the dimer-dimer interface of the PKM2 homotetramer. It is capable of activating PKM2 in cell lysate of pervanadate treated cells, which is a condition known to inhibit PKM2 activity through accumulation of phosphotyrosine peptides. ML265 significantly increased the doubling time of H1299 cells under hypoxic conditions, but interestingly showed no effect under normoxia^[1].
in vivo	ML265 gave superior plasma concentrations that persisted at higher levels over the 24 hour study. ML265 also displayed good oral bioavailability, low clearance, a long half-life and good volume of distrubtion. The 7-week mouse xenograft model (H1299 mouse xenograft) showed that the activation of PKM2 with ML265 was able to significantly reduce tumor size and occurrence without showing signs of acute toxicity. ^[1].

プロトコル(参考用のみ)

キナーゼアッセイ	PKM2 activity assay
キナーゼアッセイ	Pyruvate kinase activity is measured by monitoring pyruvate-dependent conversion of NADH to NAD+ by lactate dehydrogenase (LDH). Briefly, for cell line experiments, the medium is replaced with fresh medium 1 hr prior to the start of treatment with DMSO or activator. Also, where indicated, 100 μM pervanadate is added 10 min prior to cell lysis. Cells are lysed on ice with RIPA buffer containing 2 mM DTT and protease inhibitors and clarified by centrifugation at 21,000 × g. 5 μL of the supernatant is used to assess pyruvate kinase activity. Pyruvate kinase activity was subsequently normalized for total protein content.
細胞アッセイ	細胞株	H1299 cells
	濃度	50 μM
	反応時間	1 h
	実験の流れ	H1299 cells incubated with 50 μM ML265 for 1 hour, lysed followed by 2-D electrophoresis, Western blot and PGAM1 antibody staining.
動物実験	動物モデル	Male Balb/c mice
	投薬量	IV: 1 mg/kg, PO: 10 mg/kg; IP: 10 and 50 mg/kg
	投与方法	IV, IP and PO

参考

[1] Martin J, et al. ML265: A potent PKM2 activator induces tetramerization and reduces tumor formation and size in a mouse xenograft model. 2012 Mar 16 [Updated 2013 May 8]. In: Probe Reports from the NIH Molecular Libraries Program [Internet].

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：

Understanding the molecular pathway of triclosan-induced ADHD-like behaviour: Involvement of the hnRNPA1-PKM2-STAT3 feedback loop [ Environ Int, 2024, 191:108966]	PubMed: 39167854
Pyruvate kinase M2 regulates kidney fibrosis through pericyte glycolysis during the progression from acute kidney injury to chronic kidney disease [ Cell Prolif, 2024, 57(2):e13548]	PubMed: 37749923
Glycolysis drives STING signaling to facilitate dendritic cell antitumor function [ J Clin Invest, 2023, 133(7)e166031]	PubMed: 36821379
Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis [ Mol Cell, 2022, S1097-2765(22)00541-X]	PubMed: 35752173
Rewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRASG12D glycolytic colorectal tumors [ Commun Biol, 2022, 5(1):1159]	PubMed: 36316440
Renoprotection of Microcystin-RR in Unilateral Ureteral Obstruction-Induced Renal Fibrosis: Targeting the PKM2-HIF-1α Pathway [ Front Pharmacol, 2022, 13:830312]	PubMed: 35754468
Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation [ Eur J Pharmacol, 2022, 936:175352]	PubMed: 36309049
Cynaroside prevents macrophage polarization into pro-inflammatory phenotype and alleviates cecal ligation and puncture-induced liver injury by targeting PKM2/HIF-1α axis [ Fitoterapia, 2021, 152:104922]	PubMed: 33984439

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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