Research groups such as Tokyo Institute of Technology have integrated drug discovery targets for trypanosomatidae parasites that cause Chagas disease and leishmaniasis among the 20 disease groups "neglected tropical diseases" that WHO aims to control. Discovered by utilizing the type database "iNTRODB".We found four more hit compounds.It was successful with a hit rate that was more than 4 times higher than that of conventional drug discovery methods.
"Neglected Tropical Diseases" (NTDs) are a group of 20 diseases centered on infectious diseases caused by viruses, bacteria, parasites, etc. that are prevalent mainly in the tropical regions of developing countries and the poor.It is said that more than 10 billion people are infected in the world, and the lack of access to necessary medical care is not only a health problem but also a hindrance to economic activities.
This time, the research group will utilize the integrated database "iNTRODB" for NTDs drug discovery research developed in 2012 in collaboration with Professor Yasushi Akiyama, Professor Kiyoshi Kita, and the Astellas Pharma Pharmaceuticals Tropical Infectious Diseases Research Team to create tripanosoma parasites. The drug target "Spermidine synthase" was determined.
Next, we discovered four hit compounds with inhibitory activity against spermidine synthase by so-called "smart drug discovery" that combines docking simulation, molecular dynamics simulation, and in vitro test using the supercomputer TSUBAME of Tokyo Institute of Technology. bottom.Compared to the hit rate of 4% or less with the conventional drug discovery method, this method achieved a hit rate of 0.1%, which is more than 2.27 times higher.
It is said that drug discovery requires a long period of more than a dozen years and a huge cost of more than 3000 billion yen.In the future, the research group will actually confirm the protozoan activity of the hit compounds found this time, and will apply smart drug discovery methods to other diseases by linking IT drug discovery and biochemical experiments. The company plans to proceed and reduce drug discovery costs.
Paper information:[Scientific Reports] In silico, in vitro, X-ray crystallography, and integrated strategies for discovering spermidine synthase inhibitors for Chagas disease
