Rapamycin

Comprehensive article on Rapamycin

Rapamycin, also known as sirolimus, is a macrolide compound with potent immunosuppressive and antiproliferative properties. It was first discovered in 1972 from a soil sample collected on Easter Island (Rapa Nui), which is the origin of its name. Rapamycin is primarily used to prevent organ transplant rejection and is being studied for its potential in treating various diseases, including cancer and age-related conditions.

Mechanism of Action

Rapamycin exerts its effects by inhibiting the mammalian target of rapamycin (mTOR), a serine/threonine kinase that regulates cell growth, proliferation, motility, and survival. mTOR is a central component of the PI3K/AKT/mTOR pathway, which is critical for cellular responses to nutrients, growth factors, and stress. By inhibiting mTOR, rapamycin effectively halts the progression of the cell cycle from the G1 to the S phase, thereby reducing cell proliferation.

Clinical Uses

Rapamycin is primarily used in the following clinical settings:

• Organ Transplantation: Rapamycin is used to prevent rejection in organ transplant recipients, particularly kidney transplants. It is often used in combination with other immunosuppressants such as cyclosporine and corticosteroids.

• Cancer Therapy: Due to its antiproliferative effects, rapamycin and its analogs (rapalogs) are being investigated for the treatment of various cancers, including renal cell carcinoma and breast cancer.

• Coronary Stent Coating: Rapamycin is used in drug-eluting stents to prevent restenosis, the re-narrowing of blood vessels after angioplasty.

• Potential Anti-Aging Effects: Recent studies suggest that rapamycin may extend lifespan and delay age-related diseases in animal models, although its effects in humans are still under investigation.

Side Effects

Common side effects of rapamycin include:

• Hyperlipidemia
• Hypertension
• Anemia
• Thrombocytopenia
• Delayed wound healing

Patients on rapamycin require regular monitoring of blood levels and renal function to manage these side effects effectively.

Pharmacokinetics

Rapamycin is administered orally and has a bioavailability of approximately 14%. It is extensively metabolized in the liver by the cytochrome P450 enzyme CYP3A4. The drug has a long elimination half-life of 57 to 63 hours, allowing for once-daily dosing. It is primarily excreted in the feces.

Research and Development

Ongoing research is exploring the use of rapamycin in:

• Neurodegenerative Diseases: Investigating its potential to slow the progression of diseases such as Alzheimer's and Parkinson's.
• Metabolic Disorders: Studying its effects on conditions like diabetes and obesity.
• Longevity Studies: Examining its role in extending lifespan and improving healthspan in various organisms.

Also see

• mTOR pathway
• Immunosuppressive drugs
• Organ transplantation
• Cancer treatment
• Drug-eluting stent