TEPP-46

• CAT Number: I000849
• CAS Number: 1221186-53-3
• Molecular Formula: C17H16N4O2S2
• Molecular Weight: 372.5
• Purity: ≥95%
• Synonyms: ML-265; ML265; 6-[(3-aminophenyl)methyl]-4,6-dihydro-4-methyl-2-(methylsulfinyl)-5H-thieno[2’,3’:4,5]pyrrolo[2,3-d]pyridazin-5-one
• Target: Pyruvate Kinase
• Solubility: DMSO: ≥ 31 mg/mL
• Storage: Store at -20°C
• IC50: 92 nM (AC50)
• InChIKey: ZWKJWVSEDISQIS-UHFFFAOYSA-N

TEPP-46 (CAT: I000849) is a potent and selective activator of pyruvate kinase M2 (PKM2), a key enzyme in glycolysis. It promotes the tetrameric form of PKM2, enhancing its enzymatic activity and leading to increased glucose metabolism and ATP production. This activation of PKM2 can have implications for various physiological and pathological processes, including cancer metabolism. TEPP-46 has shown potential as a therapeutic agent for targeting metabolic reprogramming in cancer cells, making it a promising candidate for cancer treatment and further research.

Reference

1. ML265: A potent PKM2 activator induces tetramerization and reduces tumor
formation and size in a mouse xenograft model.

Walsh MJ, Brimacombe KR, Anastasiou D, Yu Y, Israelsen WJ, Hong BS, Tempel W,
Dimov S, Veith H, Yang H, Kung C, Yen KE, Dang L, Salituro F, Auld DS, Park HW,
Vander Heiden MG, Thomas CJ, Shen M, Boxer MB.
In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda
(MD): National Center for Biotechnology Information (US); 2010-.
2012 Mar 16.

Cancer cells have altered metabolic processes compared to normal differentiated
cells and the expression of the M2 isozyme of pyruvate kinase (PKM2) plays an
important role in this aberrant metabolism. The M1 isoform is a highly active
enzyme typically expressed in muscle and brain tissue, the alternatively spliced
M2 variant is considerably less active and expressed in many tumors studied to
date. This report describes the use of the PKM2 activator, ML265, and details
some of the biophysical, ex vivo and in vivo activity of this compound. ML265
induces the more active tetrameric state of PKM2 and the X-ray co-crystal
structure shows that the activator binds at the dimer-dimer interface between two
subunits of PKM2. This compound was tested in a H1299 mouse xenograft model and
showed significant reduction in tumor size, weight, and occurrence with no
apparent toxicity over the 7-week experiment.