TEPP-46 (ML-265): Research and application prospects of a selective PKM2 activator
Overview
TEPP-46 (also known as ML-265) is a highly efficient and selective conformational activator of pyruvate kinase M2 (PKM2), with the chemical formula C17H16N4O2S2, molecular weight 372.46, and CAS number 1221186-53-3. As an important tool compound in the field of metabolic research, TEPP-46 has shown significant value in cancer research, immune metabolism, and metabolic disease research.
Chemical properties
Chemical name: TEPP-46 (ML-265)
Molecular formula: C17H16N4O2S2
Molecular weight: 372.46
CAS number: 1221186-53-3
Chemical structure: Contains a unique thienopyrimidine skeleton, which endows it with high selectivity and biological activity
Mechanism of action and pharmacological properties
TEPP-46 selectively activates the tetramer form of pyruvate kinase M2 (PKM2), promotes glycolytic flux, and regulates metabolic reprogramming in cancer cells. Unlike traditional PKM2 inhibitors, TEPP-46 as a conformational activator has the following characteristics:
- High selectivity: The selectivity for PKM2 is significantly higher than that for PKM1 and other kinases
- Mechanism of conformational activation: binding to the PKM2 subunit interface to stabilize its highly active tetramer form
- Cell permeability: excellent cell membrane penetration ability, suitable for in vitro and in vivo research
- Metabolic regulation: By regulating PKM2 activity, it affects the accumulation of glycolytic intermediates, thereby altering cell proliferation and differentiation status
Main application areas
1. Cancer research
TEPP-46 serves as an important tool in tumor metabolism research to explore:
Molecular mechanism of Warburg effect
The role of PKM2 in tumor growth and metastasis
The interaction between metabolic reprogramming and tumor immune microenvironment
2. Immune metabolism research
Recent studies have found that TEPP-46 can be used to regulate immune cell metabolism, affecting:
T cell differentiation and function
Macrophage polarization
Regulation of inflammatory response
3. Research on metabolic diseases
In metabolic disease models such as diabetes and obesity, TEPP-46 helps researchers understand:
The relationship between metabolic enzyme activity and systemic metabolic homeostasis
Tissue-specific metabolic regulation mechanism
Experimental Usage Guide
In vitro studies
Solubility: It is recommended to use DMSO to prepare storage solution (usually 10-50 mM)
Working concentration: The commonly used concentration for cell experiments is 1-50 μ M
Processing time: According to the experimental design, it usually takes 24-72 hours to process
In vivo research
Animal models: validated in various tumor xenograft models
Administration method: intraperitoneal injection or oral administration
Dose reference: The commonly used dose in mouse models is 10-50 mg/kg
Precautions
- Storage conditions: Dry storage at -20 ° C to avoid repeated freeze-thaw cycles
- Solution stability: DMSO stock solution can be stored for several months at -80 ° C
- Experimental control: It is recommended to use appropriate negative and positive controls
- Cell type differences: Different cell lines may have varying responses to TEPP-46
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