Drug Repurposing

Abstract

In the search of safer and more effective drugs while reducing costs and increasing productivity of novel drug discovery, scientists are changing their focus to an approach known as drug repurposing. This involves finding a new therapeutic effect of an already existing drug. It is a method that can effectively be addressed in the drug discovery and development challenges of targeting different disorders. Many drugs which have failed clinical trials for not being effective in their intended therapeutic indication have also been repurposed which has been of great benefit for pharmaceutical industries. For instance, sildenafil failed its clinical trials and was repurposed and currently in use as a repurposed drug. Many methods are available for drug repurposing but in silico method is a cost effective and convenient method for drug repurposing which uses computer software to find a possible binding site of a drug within a protein. For its advantages, computational docking approach was used for the present drug repurposing study of mTOR protein, where the drugs chosen were metformin, aspirin and rosuvastatin. Autodock Vina and PyMOL was used to complete the study and it was found that aspirin and metformin have poor affinity (-5.8 kcal/mol) for this protein which is upregulated in various types of cancer such as breast cancer and ovarian cancer. On the other hand, rosuvastatin was found to have a high affinity (-7.8 kcal/mol in case of flexible docking and -10.2 kcal/mol in case of rigid docking) for mTOR and binds to the same binding pocket where the immunosuppressant and anticancer drug rapamycin binds. The study therefore indicates that rosuvastatin might have significant immunosuppressive and anticancer activity by downregulating the activity of mTOR and needs further studies to prove it.