MHY1485

Background

MHY1485 is a small, synthetic compound that activates the molecular mammalian target of rapamycin (mTOR) (1). mTOR is a Ser/Thr protein kinase that functions as an ATP and amino acid sensor to balance nutrient availability and cell growth. Cellular mTOR is a core component of both mTORC1 and mTORC2 multiprotein complexes, which regulate cell growth, proliferation, motility, and survival, as well as transcription, protein synthesis, and autophagy (2). Treatment of rat hepatocytes with MHY1485 suppressed autophagy by activating mTOR and inhibiting the fusion of autophagosomes and lysosomes (1). MHY1485 activated the mTOR-Nrf2 signaling pathway in UV-treated skin cells, preventing cell death and apoptosis. The mTOR activator suppressed UV-induced reactive oxygen species production and DNA single-strand breaks in UV-treated skin keratinocytes and fibroblasts (3). Similar treatment with MHY1485 rescued cultured osteoblasts from the cytotoxic effects of dexamethasone exposure, and increased ovarian weights, restored endocrine function, and promoted primordial follicle development in mice (4,5).