TEPP-46 (ML265)

Catalog No.S7302 Synonyms: CID-44246499, NCGC00186528

For research use only.

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.

TEPP-46 (ML265) Chemical Structure

CAS No. 1221186-53-3

Selleck's TEPP-46 (ML265) has been cited by 3 Publications

Purity & Quality Control

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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].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BL21 NHX5UYhHfW6ldHnvckBie3OjeR?= NHPQN3A1KHWP NVWxeIlGPTBibXnudy=> Ml:yRYN1cX[jdHnvckBw\iC{ZXPvcYJqdmGwdDDoeY1idiCSS12yJIV5eHKnc4Pl[EBqdiCHc3Po[ZJq[2irYTDjc4xqKEKOMkGgZZQhPCC3TTDpcoN2[mG2ZXSg[o9zKDVyIH3pcpMhdWWjc4Xy[YQhd3[ncjC0NEBucW6| M1jWd|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkSxNlA1Lz5{OU[0NVIxPDxxYU6=
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 Research:

[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 Research:

[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

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 372.46
Formula

C17H16N4O2S2

CAS No. 1221186-53-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1C2=C(C3=C1C(=O)N(N=C3)CC4=CC(=CC=C4)N)SC(=C2)S(=O)C

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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