The University of Tokyo’s Research Center for Advanced Science and Technology (RCAST), Fujitsu Limited, and Kowa Company Ltd. today announced that using IT-based drug discovery technologies, which entails computer-based virtual design and evaluation, they have successfully created new small molecule compounds that can inhibit cancer-causing “target proteins,” and that demonstrate promise against cancers that have shown resistance to existing drugs. In order to link the results of this research to the creation of new drugs, Kowa intends to improve upon the small molecule compounds discovered through this research.
Details of the Research and the Division of Responsibilities
Fujitsu and RCAST began joint research on IT-based drug discovery in June 2011, with Kowa joining in July, conducting research projects around multiple drug discovery targets. This particular joint research project began in December 2015, selecting a drug-resistant oncogenic protein as a drug discovery target. Fujitsu used IT-based drug discovery to design a small molecule compound that featured inhibitory activity(1), and then Kowa synthesized the compound and assessed its inhibitory activity in experiments. RCAST took on the role of providing information on drug discovery targets based from a medical perspective. Fujitsu and Fujitsu Laboratories Ltd. additionally made repeated improvements to the IT-based drug discovery technologies during the course of the joint research project, increasing both accuracy and performance.
Results of the Joint Research
In this joint research, Fujitsu leveraged its proprietary technologies to provide Kowa with chemical structures with the anticipated effect of decreasing the activities of the target protein. Specifically, Fujitsu incorporated drug candidate compound design technology(2) and the drug discovery insights it has previously accumulated, and designed synthetic accessible small molecule compounds using computers. Next, the binding affinity of each compound with the target protein is calculated to narrow down the selection using the M2BAR method(3), which is an improvement on high precision activity prediction technology(4). Fujitsu also took into consideration the results of high precision conformational analysis(5) based on quantum mechanics. Kowa synthesized the small molecule compounds designed by Fujitsu, and confirmed that some of the compounds demonstrated the inhibitory activity desired for drug candidates. Kowa subsequently synthesized multiple small molecule compounds sharing similar chemical structures, and confirmed that a series of the synthesized compounds also showed inhibitory activity. Kowa is currently evaluating the complex structure of these compounds using X-ray crystallography, and plans to optimize the small molecule compounds obtained from this research to reflect the results to the discovery of new drugs. Through this joint research project, RCAST, Fujitsu, and Kowa have succeeded in using IT-based drug discovery to create new small molecule compounds with inhibitory activity against cancer-causing target proteins, and may one day prove effective even against cancers that show resistance to existing drugs.
(1) Inhibitory activity The degree to which a compound binds to a protein thought to cause a specific disease indication and inhibits the function of the protein. Usually expressed in terms of the concentration of the compound.
(2) Drug candidate compound design technology Optimum Packing of Molecular Fragments (OPMF), a software module developed by Fujitsu that designs small molecule compounds that bind to the functional site of proteins that are believed to cause specific disease indications and inhibit the activity of the proteins.
(3) M2BAR A computational method developed by Fujitsu Laboratories for rapidly and accurately predicting the quantitative activity of a compound using multiple binding patterns.
(4) High-precision activity prediction technology Software developed by Fujitsu Laboratories, comprised of MAPLECAFEE, a module that, based on molecular dynamics calculations, predicts the inhibitory activity of drug candidate compounds with a high level of precision that is equivalent to that of biochemical assays, and Force Field Formulator for Organic Molecules (FF-FOM), a module that generates highly detailed parameters for calculating the forces between atoms.
(5) Conformational analysis A method of analyzing the relationship between a compound’s conformation (three-dimensional structure) and its potential energy.
About Research Center for Advanced Science and Technology
Research Center for Advanced Science and Technology (RCAST) aims to contribute to the development of science and technology by expeditiously taking on new challenges arising from the advancement of science and coincident changes in society, and by exploring new areas of advanced science and technology for the benefit of humankind and society.