OSU-53

OSU-53 is a novel, orally bioavailable small molecule dual adenosine monophosphate-activated protein kinase (AMPK) activator and mechanistic target of rapamycin (mTOR) inhibitor. Developed by researchers at The Ohio State University, OSU-53 directly stimulates AMPK kinase activity by binding to its autoinhibitory domain, while also exhibiting off-target direct inhibition of mTOR. This dual mechanism leads to the suppression of downstream mTOR/p70S6K signaling, inhibition of Akt-mediated pathways, and modulation of energy homeostasis by suppressing fatty acid biosynthesis. Preclinical studies have demonstrated that OSU-53 exhibits potent antitumor activities in vitro and in vivo, particularly in models of triple-negative breast cancer, thyroid cancer, small cell lung cancer, and multiple myeloma, by reversing the mesenchymal phenotype, suppressing epithelial-mesenchymal transition (EMT), and inducing protective autophagy.