| Summary: | 碩士 === 國立陽明大學 === 生物醫學資訊研究所 === 104 === The traditional way for drug development takes a high amount of time and cost, typically, only one out of tens of thousands of compounds is able to be approved and marketed. The Drug repositioning is aim to develop new uses of marketed drugs or new indications, including excavations poorly performing drugs at the clinical research stage. This greatly eliminates the high risk of pre-clinical failure. This study will establish a screening process by using information methods for drug repositioning screening and to identify potential drug candidates.
At the beginning, we make sure what types of diseases (indications) we want to treat, gathering a therapeutic class of diseases and analyzed these drugs. First, find the candidate drugs which had the similar chemical structure and can treat the disease. After screening, we determine whether these drugs meets the drug repositioning conditions. Second, we viewed the drugs which are original treat the diseases and seeking for the proteins that the drugs are interacted with. Then, we determined whether the drugs we screening out is able to interact with the specific proteins just like the original drugs did. Finally, when the people who are suffer from the disease, we analyzed how is the gene expression level. We used gene expression profiling to analyzed the effects of drugs to the cells. If the gene expression level is different after we introducing the drugs, which indicates the drugs might have the ability to inhibit the disease and these drugs will be our final screening candidates.
In this study, we were unable to do animal experiments. Therefore, our authentication methods rely on computational approach. In order to verify the feasibility of our approach methods, we validate the known three successful drug repositioning drugs, and whether these drugs were candidate after viewing via the screening process. Due to the limits information/partially missing data of drugs and inconsistent data libraries format which results in screening limitations. Through the screening process, the successful repositioned drug of pancreatic cancer - Paclitaxel and repositioned drug of prostate cancer - Raloxifene, were lists in the final drug candidates in the end. However, the successful repositioned drug of multiple myeloma drug – Vorinostat cannot be analyze by Connectivity Map, because it only has the up regulation of genes during the analysis.
Prediction of candidate drugs for treating pancreatic cancer, however, the mechanism of action of the three candidates, Doxorubicin, Daunorubicin and Mitoxantrone is close with the successful repositioned drug - Paclitaxel. All belong to anticancer drugs, it can be embedded in the DNA double helix and closely integrated, so that cancer cells can not carry out DNA replication and transcription. In addition to using the proposed method found the successful repositioned drug, we use this article - Pathway Analysis for Drug Repositioning Based on Public Database Mining, to confirm the feasibility of other candidate drugs for treating pancreatic cancer. According to the research method aim to find the potential drugs other than the common method, so, in addition to finding the drugs it had already found, but also identified two potential drugs that article has not been found. Moreover, the same drug with that article, which greatly increased the feasibility of the treatment of pancreatic cancer. So our study provides another method may identify more potential drugs.
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