text: Since the discovery of mTOR, much research has been done on the subject, using rapamycin and rapalogs to understand its biological functions. The clinical results from targeting this pathway were not as straight forward as thought at first. Those results have changed the course of clinical research in this field.
  Initially, rapamycin was developed as an antifungal drug against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. A few years later its immunosuppressive properties were detected. Later studies led to the establishment of rapamycin as a major immunosuppressant against transplant rejection, along with cyclosporine A. Combining rapamycin with cyclosporine A, enhanced rejection prevention in renal transplantation. Therefore, it was possible to use lower doses of cyclosporine, which minimized toxicity of the drug.
  In the 1980s the Developmental Therapeutic Branch of the National Cancer Institute (NCI) evaluated rapamycin and discovered it had an anticancer activity and was non-cytotoxic, but had cytostatic activity against several human cancer types. However, due to unfavorable pharmacokinetic properties, the development of mTOR inhibitors for the treatment of cancer was not successful at that time. Since then, rapamycin has also shown to be effective for preventing coronary artery re-stenosis and for the treatment of neurodegenerative diseases.