Definition

A topical gel formulation containing the macrolide sirolimus (rapamycin), with potential anti-proliferative and chemopreventive activities. Upon topical administration of sirolimus topical gel PTX-022, sirolimus migrates into the basal keratinocytes and is internalized by the affected cells. 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 cellular proliferation in mTOR-overexpressing cells. Additionally, by inhibiting mTOR, PTX-022 may inhibit translation of mutant keratin mRNAs and the production of mutant keratins in cells in which mutant keratin genes dysregulate keratinocyte proliferation.