Rapamycin (Sirolimus): From Natural Product to Master Regulator of Cell Growth скачать в хорошем качестве

Rapamycin (Sirolimus): From Natural Product to Master Regulator of Cell Growth

In this lecture, we explore rapamycin, a remarkable natural product originally isolated from Streptomyces species discovered on Rapa Nui (Easter Island). Once nearly discarded due to early safety concerns, rapamycin went on to become one of the most important immunosuppressive and immunomodulatory drugs in modern medicine. This talk traces rapamycin’s journey from polyketide biosynthesis and macrolactone structure to its mechanism of action via FKBP12-mediated inhibition of mTOR (mechanistic Target of Rapamycin)—a highly conserved kinase that integrates nutrient sensing, metabolism, cell growth, and immune function. Key topics covered include: Rapamycin’s biosynthetic gene cluster and comparison with erythromycin Antifungal activity and early development history The discovery of TOR/mTOR signaling and its biological roles Immunosuppression vs. immunomodulation and dose-dependent effects Clinical use in organ transplantation, cancer therapy, and FDA-approved indications Rapalogs and next-generation mTOR kinase inhibitors Rapamycin-induced autophagy and links to aging and longevity Pleiotropic effects connecting immunity, metabolism, and disease This lecture is part of an upper-division Medicinal Chemistry & Pharmacology (CH322) course and is appropriate for students and professionals interested in drug discovery, natural products, immunology, aging biology, and translational medicine.