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TEPP-46 (ML265)

Name: TEPP-46 (ML265)
Brand: Selleck Chemicals
SKU: S7302
Rating: 5 (8 reviews)

Synonyms: CID-44246499, NCGC00186528

Catalog No.S7302 Purity:99.88%

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

Purity & Quality Control

Batch: Purity: 99.88%

99.88

TEPP-46 (ML265) Related Products

Related Targets	PKM2 PMK2	Click to Expand
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Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
BL21	Function assay	4 uM	50 mins		Activation of recombinant human PKM2 expressed in Escherichia coli BL21 at 4 uM incubated for 50 mins measured over 40 mins	29641204
Click to View More Cell Line Experimental Data

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
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].
Kinase Assay	PKM2 activity assay
Kinase 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	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.

In Vivo
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].
Animal Research	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

References

[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].

Chemical Information & Solubility

Molecular Weight	372.46	Formula	C₁₇H₁₆N₄O₂S₂
CAS No.	1221186-53-3	SDF	--
Smiles	CN1C2=C(C3=C1C(=O)N(N=C3)CC4=CC(=CC=C4)N)SC(=C2)S(=O)C
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 72 mg/mL ( (193.3 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.					In vivo Formulation Calculator
	Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	3.7mg/ml (9.93mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 74 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; 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.	In vivo Formulation Calculator
Clear solution	5% DMSO 1 95% corn oil	0.6mg/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.
Clear solution	5% DMSO 1 95% corn oil	0.6mg/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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	3.75mg/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 40%PEG300 2 5%Tween80 3 50%ddH2O	3.7mg/ml (9.93mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 74 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; 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.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

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.

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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