Definition

A topical gel formulation containing the macrolide sirolimus (rapamycin), with potential anti-proliferative activity. Upon topical administration of sirolimus topical gel NPC-12Y, sirolimus is internalized by the affected cells in the skin. In turn, sirolimus binds to the immunophilin FK binding protein-12 (FKBP-12) and forms a sirolimus-FKBP-12 complex. This complex binds to and inhibits the activity of the serine/threonine kinase mammalian target of rapamycin (mTOR) and the mTOR-mediated signaling pathways, which reduces cell proliferation. mTOR, a serine/threonine kinase belonging to the phosphatidylinositol-3 (PI3K) kinase-related kinase (PIKK) family, plays an important role in the PI3K/Akt/mTOR signaling pathway that regulates cell growth and proliferation, and its expression or activity is frequently dysregulated in human cancers.