TEPP-46 (ML265)

製品コードS7302 バッチS730202

印刷

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

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。	3.750mg/ml (10.07mM)	Taking the 1 mL working solution as an example, add 50 μL of 75 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL 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。	0.600mg/ml (1.61mM)	Taking the 1 mL working solution as an example, add 50 μL of 12 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	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	TEPP-46 (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. It binds at the dimer-dimer interface of the PKM2 homotetramer and 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. This compound significantly increased the doubling time of H1299 cells under hypoxic conditions, but interestingly showed no effect under normoxia^[1].
in vivo	In a 24-hour study, TEPP-46 (ML265) gave superior plasma concentrations that persisted at higher levels. It 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 activation of PKM2 with this compound 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 this compound. 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 TEPP-46 (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

https://www.ncbi.nlm.nih.gov/books/NBK153222/

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：

A novel pathway for stemness propagation and chemoresistance in non-small cell lung cancer via phosphorylated PKM2-loaded small extracellular vesicles [ Theranostics, 2025, 15(8):3439-3461]	PubMed: 40093893
UCHL3 augments cuproptosis via PKM2 deubiquitination in hepatocellular carcinoma [ Free Radic Biol Med, 2025, 237:65-75]	PubMed: 40451468
Triclosan exposure induces liver fibrosis in mice: The heterogeneous nuclear ribonucleoprotein A1/pyruvate kinase M2 axis drives hepatic stellate cell activation [ Ecotoxicol Environ Saf, 2025, 294:118113]	PubMed: 40157328
Pyruvate kinase M2 activation maintains mitochondrial metabolism by regulating the interaction between HIF-1α and PGC-1α in diabetic kidney disease [ Mol Med, 2025, 31(1):266]	PubMed: 40713487
Pyruvate kinase modulates the link between β-cell fructose metabolism and insulin secretion [ FASEB J, 2025, 39(7):e70500]	PubMed: 40151947
An adult clock regulator links circadian rhythms to pancreatic β-cell maturation [ bioRxiv, 2025, 2023.08.11.552890]	PubMed: 37609178
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
PKM2-mediated STAT3 phosphorylation promotes acute liver failure via regulating NLRP3-dependent pyroptosis [ Commun Biol, 2024, 7(1):1694]	PubMed: 39722076
Glycolysis drives STING signaling to facilitate dendritic cell antitumor function [ J Clin Invest, 2023, 133(7)e166031]	PubMed: 36821379

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。