I had earlier illustrated an christian louboutin outlet uk for drug repurposing using the drug Rabeprazole. Recently, I came across an interesting paper that discussed repurposing of drugs for cancer and thought it would be interesting to see if some of these results could be reproduced using DistilBio (1).
Two of the drugs, and , from the paper are used here to illustrate the use of DistilBio as an initial tool for drug repurposing. Losartan is an anti-hypertensive and here anti-arrhythmic agent while Procainamide is an anti-arrhythmic agent with different targets.
Let’s look at Losartan first.
The query I ran is as follows christian louboutin sale uk to find the protein targets of Losartan and the biological processes.http://www.theblc.co.uk/
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Query: losartan > protein > Go-biological process
The results are as follows:
The details tab for Losartan shows that this is a drug targeting the Angiotensin receptor II. I filtered the protein targets by the source and selected the source as DrugBank. Generally, DrugBank data gives us the primary targets of drugs. is the target for losartan and I had a look at the biological processes associated with the protein. Calcium mediated signalling, Cell growth, Cell proliferation, Inflammatory response are some of the biological processes associated with AGTR1. These are known processes that play a role in cancer. I further extended the query by selecting AGTR1_Human to find the proteins interacting with AGTR1 and their biological processes.
The query reads as:
Query: AGTR1_Human > protein > Go-biological process
The results are as follows:
Again, you can see that proteins like interact with AGTR1. These are proteins that have been in implicated in cancer. (2-4). Also, looked at the biological processes and some of them are epidermal growth factor receptor signaling pathway, fibroblast growth factor receptor signaling pathway, positive regulation of ERK1 and ERK2 cascade, positive regulation of angiogenesis, positive regulation of endothelial cell migration, positive regulation of epithelial cell migration, processes that may play a role in cancer.
The other drug is procainamide. I ran a query similar to the query for Losartan.
Query: Procainamide > protein > Go-biological process
The result is below.
Again, filtered the results by DrugBank. Procainamide is a sodium channel blocker and the primary target is sodium channel The drug also targets . The processes associated with DNMT1 are DNA methylation, Positive expression of gene expression, Transcription, DNA dependant, Chromatin modification. These again may play a role in development of cancer.
I further extended the query to find the drugs targeting DNMT1 and also the diseases related to these drugs.
Query: DNMT1_Human > drug > disease (related)
The diseases associated with the drugs targeting DNMT1 are Neoplasms of the Breast, Prostate, Colon, Colorectum, Head and Neck, Lung, Pancreas, Stomach, Carcinoma and Leukemia like Myeloid, Acute, CML.
The results again are interesting that the drugs targeting DNMT1 are anti-cancer drugs which indicate that DNMT1 may play a role in cancer.
Therefore the question that arises is “Can these drugs be repurposed as anti-cancer drugs?” Further studies could perhaps reveal the anti-cancer properties of these drugs.
The above examples look at 2 different concepts in drug repurposing –
- Primary target of a drug that may play a role in cancer apart from its role in disease for which the drug has been approved and
- Off-target of a drug that may play a role in cancer.
Hence using DistilBio as an initial tool, a researcher can find novel interactions between drugs, diseases and targets.
- The prince and the pauper. A tale of anticancer targeted agents.
- Jak2 tyrosine kinase and cancer: how good cells get HiJAKed.
- Phospholipase Cgamma1 is required for metastasis development and progression.
- The tyrosine phosphatase Shp2 (PTPN11) in cancer.