ML-265

Territorial Availability: Available through Bertin Technologies only in France

• Synonyms
  • 6-[(3-aminophenyl)methyl]-4,6-dihydro-4-methyl-2-(methylsulfinyl)-5H-thieno[2’,3’:4,5]pyrrolo[2,3-d]pyridazin-5-one
• Correlated keywords
  • aerobic glycolysis pyruvate kinases PKM2 antitumors antiproliferation activators anticancers anti-tumors anti tumors cancers anti-cancers anti-proliferation proliferation ML265 MSLs 265 tumor-specific PKMs PKM-2 2 two fructose-1,6-bisphosphate 1,6-FBP FBPs binding binds binders dimer-dimer dimers interfaces tetramerization isoforms reduces reduction H1299 H-1299 Hs 1299 cells xenografts lungs carcinoma CIDs CID-44246499 CID44246499 NCGC-00186528 NCGCs 00186528 NCGC00186528 186528 TEPPs TEPP46 TEPP-46 46 metabolism catalyzes final steps formations ATP phosphoenolpyruvate phosphosenol ADP expressions M2 M 2 isozymes PK metabolic reprogramming glucose allosterically allosteric regulated regulates upstream up-stream up streams glycolytic intermediates fructose 1 6 bisphosphate one six feed forward mechanisms phosphorylated states peptides motifs tyrosines inhibits inhibitors inhibitions activity releases sites ML-265 specific subunits inducing induces active forms enzymes folds selectivity PKM1 PKR PKL PRM-1 M1 1 sizes weights occurrences mice models humans non-small nonsmall non small
• Product Overview:
  Pyruvate kinase catalyzes the final step in glycolysis, the formation of pyruvate and ATP from phosphoenolpyruvate and ADP. The expression of the M2 isozyme of pyruvate kinase (PKM2) plays an important role in the metabolic reprogramming of tumor cells, which require high amounts of glucose for proliferation. PKM2 is allosterically regulated by the upstream glycolytic intermediate, fructose-1,6-bisphosphate (FBP), which controls glycolysis in a feed forward mechanism.{21504} Whereas cancer cells exist in highly phosphorylated states, the binding of certain peptide motifs with phosphorylated tyrosines can inhibit PKM2 activity by causing the release of FBP from the allosteric site.{21504} ML-265 activates tumor-specific PKM2 (EC50 = 92 nM) by binding to the dimer-dimer interface between two subunits of PKM2 and inducing tetramerization, which is the most active form of the enzyme.{24497} It demonstrates >100-fold selectivity for PKM2 over the related PKM1, PKR, and PKL isoforms.{24497} At 50 mg/kg, ML-265 has been shown to reduce tumor size, weight, and occurrence in mice bearing H1299 cell xenografts in a model of human non-small cell lung carcinoma.{24497}