TEPP-46 est un activateur puissant et sélectif de pyruvate kinase M2 (PKM2) avec un AC50 de 92 nM, montrant peu ou pas d'effet sur PKM1, PKL et PKR.
TEPP-46 ist ein potenter und selektiver Pyruvatkinase M2 (PKM2) -Aktivator mit einem AC50 von 92 nM, der nur geringe oder keine Auswirkungen auf PKM1, PKL und PKR zeigt.
TEPP-46 (ML-265) is a potent and selective pyruvate kinase M2 (PKM2) activator with an AC50 of 92 nM, showing little or no effect on PKM1, PKL and PKR.
For research use only. We do not sell to patients.
TEPP-46 Chemical Structure
CAS No. : 1221186-53-3
This product is a controlled substance and not for sale in your territory.
Based on 40 publication(s) in Google Scholar
TEPP-46 purchased from MedChemExpress. Usage Cited in:
Cell Rep. 2020 May 26;31(8):107690.
[Abstract]
Immunofluorescence of PKM2 in DCs. When added TEPP-46 to prevent the dissociation of PKM2 tetramers, LPS-induced accumulation of nuclear PKM2 as well as IL-12 expression is diminished.
TEPP-46 purchased from MedChemExpress. Usage Cited in:
Cell Rep. 2020 May 26;31(8):107690.
[Abstract]
Analysis of enzymatic activity of PKM2. Protein level of PKM2 is analyzed using Western Blotting.
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Description
TEPP-46 (ML-265) is a potent and selective pyruvate kinase M2 (PKM2) activator with an AC50 of 92 nM, showing little or no effect on PKM1, PKL and PKR[1].
In Vitro
TEPP-46 and DASA-58 activate PKM2 by a mechanism similar to that of the endogenous activator FBP. Pre-treatment of cells with TEPP-46 or DASA-58 prevents pervanadate-induced inhibition of PKM2 activity. TEPP-46 also induces a decrease in the intracellular levels of acetyl-coA, lactate, ribose phosphate and serine[1]. TEPP-46 inhibits LPS-induced Hif-1α and IL-1β, as well as the expression of a range of other Hif-1α-dependent genes. TEPP-46 treatment significantly downregulates the expression of the M1 markers Il12p40 and Cxcl-10. Activation of PKM2 using TEPP-46 significantly inhibits FSL-1 and CpG-induced Il1b mRNA expression. TEPP-46 inhibits Mtb-induced Il1b mRNA levels, boosts Mtb-induced levels of Il10 mRNA, and has no effect on levels of Tnf[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
TEPP-46 Related Antibodies
In Vivo
TEPP-46 exhibits good oral bioavailability with relatively low clearance, long half-life, and good volume of distribution-parameters that predict for drug exposure in tumor tissues. TEPP-46 at 150 mg/kg readily achieves maximal PKM2 activation measured in A549 xenograft tumors[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Room temperature in continental US; may vary elsewhere.
Storage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
2 years
-20°C
1 year
Solvent & Solubility
In Vitro:
DMSO : 50 mg/mL (134.24 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.6849 mL
13.4243 mL
26.8485 mL
5 mM
0.5370 mL
2.6849 mL
5.3697 mL
10 mM
0.2685 mL
1.3424 mL
2.6849 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 3
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (6.71 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 4
Add each solvent one by one: 10% DMSO 90% Corn Oil
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution.
If precipitation or phase separation occurs during preparation,
heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 10 mg/mL (26.85 mM); Suspended solution; Need ultrasonic
Protocol 2
Add each solvent one by one: 0.5% CMC-Na/saline water
Solubility: 5 mg/mL (13.42 mM); Suspended solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[2]. Palsson-McDermott EM, et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015 Jan 6;21(1):65-80.
[Content Brief]
Cell Assay
[1]
2,000 cells are seeded in 96-well plates 24 h prior to treatment start. CellTiter96® AQueous is used to assess cell viability following oxidant and PKM2 activator combination treatments. MTS: (3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium).
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]
H1299 parental and H1299 cells with constitutive expression of a mouse PKM1 cDNA (H1299-PKM1 cells) are propagated in RPMI supplemented with 10% fetal bovine serum, 2 mM glutamine, and hygromycin for transgene selection. Cells are harvested, resuspended in sterile PBS, and 5×105 cells are injected subcutaneously into nu/nu mice. Tumor growth is monitored by caliper measurement, the mice are sacrificed and tumors harvested after the time indicated. Tumors are weighed, divided and either flash-frozen in liquid nitrogen or fixed in formalin for later analysis.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
[2]. Palsson-McDermott EM, et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015 Jan 6;21(1):65-80.
[Content Brief]
[1]. Anastasiou D, et al. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol. 2012 Oct;8(10):839-847.
[2]. Palsson-McDermott EM, et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell Metab. 2015 Jan 6;21(1):65-80.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
2.6849 mL
13.4243 mL
26.8485 mL
67.1213 mL
5 mM
0.5370 mL
2.6849 mL
5.3697 mL
13.4243 mL
10 mM
0.2685 mL
1.3424 mL
2.6849 mL
6.7121 mL
15 mM
0.1790 mL
0.8950 mL
1.7899 mL
4.4748 mL
20 mM
0.1342 mL
0.6712 mL
1.3424 mL
3.3561 mL
25 mM
0.1074 mL
0.5370 mL
1.0739 mL
2.6849 mL
30 mM
0.0895 mL
0.4475 mL
0.8950 mL
2.2374 mL
40 mM
0.0671 mL
0.3356 mL
0.6712 mL
1.6780 mL
50 mM
0.0537 mL
0.2685 mL
0.5370 mL
1.3424 mL
60 mM
0.0447 mL
0.2237 mL
0.4475 mL
1.1187 mL
80 mM
0.0336 mL
0.1678 mL
0.3356 mL
0.8390 mL
100 mM
0.0268 mL
0.1342 mL
0.2685 mL
0.6712 mL
TEPP-46 Related Classifications
Metabolic Enzyme/Protease
Pyruvate Kinase
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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