Rapamycin was initially investigated as an antibiotic, but then it was found to have immunomodulation properties (it can decrease or increase the immune system function). It was ultimately approved for the prevention of allograft rejection in recipients of organ transplants.
In addition to this application, preclinical and early clinical studies showed that rapamycin alone and in combination inhibited tumor cell proliferation, suppressed tumor angiogenesis, and induced apoptosis (cell death) of some cancer cells.
However, as the patent on rapamycin was about to expire and extensions were being reviewed, it was no longer financially feasible to continue its development as a cancer therapeutic. As such, other mTOR inhibitor products began to be developed that could be patented.
Rapamycin was first approved for sale by the FDA in 1999. The patent for rapamycin expired in 2013 and the first generic version of the medication became available in the USA in 2019.
Since it was first discovered, companies have put their own brand names on their products, and a generic drug name “sirolimus” was established.
Here is a listing of the different names rapamycin is known by:
Generic Name: Sirolimus
- Pfizer Rapamune
- Wyeth Rapamune
Generic Manufacturers of Rapamycin / Sirolimus:
- Glenmark Pharmaceuticals Sirolimus
- Zydus Siromus
- Biocon Rapacan
- Rocas Sirolimus
- Panacea Biotec - Siropan sirolimus
- Actiza Sirolimus
- Dr. Reddy’s Sirolimus
There are also drugs that are identified by the general term “Rapalogs” (a word formed from the “Rapa” from rapamycin, and “analogues” which in a compound with a molecular structure closely similar to that of another). These drugs that function virtually identically to the way rapamycin works (ie. targets the same receptors) and therefore have the same functional benefits.
Researchers have modified the structure of rapamycin to prepare numerous analogues, typically so that they can patent it for sale as a small molecule drug. In theory these drugs should provide the same life extension benefits as rapamycin, but this has not yet been confirmed in studies with animals.
The two main rapalogs on the market today are:
The patent on Novartis Afinitor (everolimus) has expired and generic versions of the drug are now approved and starting to become available at low cost.
Generic Manufacturers of Everolimus:
- Glenmark Pharmaceuticals - Evermil (Everolimus) Tablets (5mg and 10mg)
- Zydus Everomus (Everolimus) - (5mg and 10mg)
- Biocon Evertor (Everolimus): tablets are available in 2.5 mg, 5 mg, 7.5 mg and 10 mg
- Cipla Rolimus (Everolimus)
- Natco Rampact Everolimus
- BDR Pharmceutical Ltd Everbliss (Everolimus) - 5mg, 10mg
- Bruck Pharmaceuticals Afilimus (Everolimus) - 5mg
- Beacon pharma, Xevirol (Everolimus 5mg)
- Hikma Everolimus, 2.5mg, 5mg, 7.5mg, 10mg
- Par Pharmaceuticals Everolimus, 1mg, 2.5mg, 5mg, 7.5mg
All of these drugs are what are classed as MTOR inhibitors - drugs that block the MTOR1 pathway, and can also disrupt the MTORC2 pathway if used at high doses for long periods of time. Currently it is generally believed that most of the lifespan benefits come from inhibiting MTOR1, and most of the negative side effects of the medications from blocking MTOR2 - but this remains an active area of research.
Companies working on developing a new generation of MTOR inhibitors include: