Drug Repositioning - BiopharmaDirect

Drug Repositioning

Drug reuse (also called drug rediscovery or drug relocation) refers to rediscovery of new indications for existing drugs. One of the most famous examples is sildenafil, whose purpose is to treat angina pectoris, and later found that it can also treat erectile dysfunction. Other examples include minoxidil, a drug that is designed to treat ulcers but can eventually treat high blood pressure and hair loss. Thalidomide (thalidomide) was used to treat pregnant women in the 1950s, and was approved for the treatment of multiple myeloma in 2006. Thioguanine, originally developed for leukemia, was re-used as a rescue immunosuppressive agent for the treatment of inflammatory bowel disease (IBD). Reusing drugs is of great significance. Not only does it take less time, but it is also less expensive. Compared to redeveloping a new drug, it costs less money. At the same time, it also reduces the risk of new side effects. Based on computer-aided drug design and AI technology, advanced solutions have been applied for drug reuse.

The idea of drug reuse is roughly as follows:

The first three are the construction of molecular structure, and the latter three are the macroscopic similarity analysis of drugs. Through the above six aspects of research, we can further determine the feasibility of drug reuse.

In the process of drug research, it is very important to understand the target relationship of drugs. With the increase of available data in many public databases, many calculation methods to predict the relationship between drug targets have also been proposed. The main idea is to establish appropriate drug target data, construct a method for predicting the relationship of action and make a reasonable evaluation, and then predict the actual relationship of action. These calculation methods make up for the shortcomings of time consumption and high cost investment in the experimental method. To realize the new use of old drugs, we must first re-determine the new targets of the old drugs.

1. Use the Batman-TCM analysis platform to obtain information on the chemical composition of drugs online to obtain possible targets, and select high-confidence proteins as targets. Due to the problem of naming irregularities in the retrieved targets, you can use the UniProtKB search function in the UniProt database to correct all the retrieved proteins to their official names by entering the protein name and restricting the species to human. Conversion operation to obtain target information related to active ingredients.

2. After predicting the target, the target is screened, and the target protein containing the exact activity is summarized.

3. According to the above prediction and screening results, remove the chemical components without corresponding targets, and delete the duplicate targets. Import the data into Cytoscape to construct the following network:

(1) The drug component target network. If a certain protein is the target of the drug, the two are connected to each other in the network.

(2) Use the String 10.0 tool to construct a common target protein-protein interaction network (PPI) and a drug-specific target PPI.

Finally, the topology analysis and module analysis of the common target PPI network are carried out. At the same time, the targets are ranked and scored according to the component-target and PPI network. The marketed medicine components or targets are represented as nodes in the network, and the mutual relationship between them is represented by edges.

The shared target and the unique target are derived from the target attribute Explain the scientific connotation of "new use of old medicine" from the perspective.