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

Описание: 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.