ML265

Research use only, not for human use.

ML265 is a potent PKM2 activator (AC50 : 92 nM) showing little or no effect on PKM1 PKL and PKRinduces tetramerization and reduces tumor formation and size in a mouse xenograft model. .

ML265 is a potent PKM2 activator (AC50 : 92 nM) showing little or no effect on PKM1 PKL and PKRinduces tetramerization and reduces tumor formation and size in a mouse xenograft model. (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. 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.(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.

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. 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.

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.

TEPP-46

Others

Other Targets

PKM2

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1221186-53-3

372.46

C17H16N4O2S2

>98% (HPLC)

DMSO:50 mg/mL (134.24 mM)

Cn1c2cc(sc2c2cnn(Cc3cccc(N)c3)c(=O)c12)S(C)=O

6-(3-aminobenzyl)-4-methyl-2-(methylsulfinyl)-46-dihydro-5H-thieno[2'3':45]pyrrolo[23-d]pyridazin-5-one

(-20℃)

With Ice Pack

≥ 2 years