TEPP-46 (ML265)

Catalog No.S7302 Batch:S730202

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Technical Data

Formula

C17H16N4O2S2
Molecular Weight 372.46 CAS No. 1221186-53-3
Solubility (25°C)* In vitro DMSO 74 mg/mL (198.67 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
3.75mg/ml 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 95% corn oil
0.6mg/ml 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
PKM2 [1]
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].

Protocol (from reference)

Kinase Assay:

[1]
  • PKM2 activity assay

    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.
Cell Assay:

[1]
  • Cell lines

    H1299 cells

  • Concentrations

    50 μM

  • Incubation Time

    1 h

  • Method

    H1299 cells incubated with 50 μM ML265 for 1 hour, lysed followed by 2-D electrophoresis, Western blot and PGAM1 antibody staining.
Animal Study:

[1]
  • Animal Models

    Male Balb/c mice

  • Dosages

    IV: 1 mg/kg, PO: 10 mg/kg; IP: 10 and 50 mg/kg

  • Administration

    IV, IP and PO

Selleck's TEPP-46 (ML265) has been cited by 7 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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