TEPP-46 is a potent and selective activator of recombinant pyruvate kinase M2 (PKM2) with half-maximum activating concentration (AC50 value) of 92 nM, and has little or no effect on PKM1, PKL and PKR.
TEPP-46 (ML-265) is an effective and specific activator of pyruvate kinase M2 (PKM2), demonstrating an AC50 of 92 nM, while showing minimal to no impact on PKM1, PKL, and PKR[1].
体内研究
TEPP-46 is characterized by favorable oral bioavailability, low clearance, an extended half-life, and an effective volume of distribution, which are indicative of its potential drug exposure in tumor tissues. Administered at a dose of 150 mg/kg, TEPP-46 effectively maximizes PKM2 activation in A549 xenograft tumors[1].
体外研究
TEPP-46, along with DASA-58, activates PKM2 through a mechanism akin to that of the natural activator FBP. Cells pretreated with TEPP-46 or DASA-58 are protected from pervanadate-induced inhibition of PKM2 activity. Furthermore, TEPP-46 leads to reduced intracellular levels of acetyl-coA, lactate, ribose phosphate, and serine[1].
TEPP-46 also curbs the induction of Hif-1α and IL-1β by LPS, as well as the expression of various Hif-1α-dependent genes. The treatment significantly suppresses the expression of M1 markers Il12p40 and Cxcl-10. By activating PKM2, TEPP-46 notably inhibits FSL-1 and CpG-induced Il1b mRNA expression, reduces Mtb-induced Il1b mRNA levels, increases Mtb-induced Il10 mRNA levels, and does not affect Tnf levels[2].
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