ASP4132

ASP4132 is an orally active, potent small molecule activator of adenosine monophosphate-activated protein kinase (AMPK). It has been developed as a clinical candidate for the treatment of human cancers, including non-small cell lung cancer and breast cancer. Mechanistically, ASP4132 activates AMPK signaling, leading to downstream inhibition of mTORC1, degradation of receptor tyrosine kinases such as PDGFRα and EGFR, Akt inhibition, autophagy induction, and apoptosis in tumor cells. Additionally, it acts as a mitochondrial complex I inhibitor affecting oxidative phosphorylation in metabolically active cells. Preclinical studies have shown that ASP4132 inhibits tumor growth in xenograft models. In phase I clinical trials for advanced solid tumors, the drug demonstrated limited clinical activity with dose-limiting toxicities at higher doses[1][3][4][5][6].