The drug discovery chemistry platform unit performs “Hit to Lead” optimization of HTS hits identified in the Drug discovery seed compound exploratory unit, where chemical structures of the HTS hits are synthetically modified for improved in vitro activity, selectivity and pharmacokinetics in order to verify desired in vivo efficacy in animal disease models. In the “Hit to Lead” stage, applications of the latest drug discovery technologies such as in silico docking simulations by the Drug discovery computational chemistry platform unit, and X-ray crystallographic analysis by the Drug discovery structural biology platform unit proved particularly effective. Lead compounds identified in this process are further optimized for in vivo efficacy and toxicity profiles (“Lead optimization”) for preclinical candidate identification.
Click on the following image to enlarge
Over the years, our group has worked on several epigenomic enzyme targets in cancer drug discovery and frequently came across lack of in vivo efficacy despite potent in vitro activities. We now suspect the lack of in vivo efficacy observed may be attributed to multi-functionality of the target protein and that inhibition of only one of many functions of the target may not lead to the desired anti-cancer activity in vivo. Targeted protein degradation (TPD or PROTACs) is an emerging modality in small (or medium-sized) molecule drug discovery, in which the target protein is degraded by the ubiquitin-proteasome system and all the functions of the target will be removed from the system. We are currently applying TPD to an epigenomic enzyme target and planning to expand our efforts to other target proteins and indications.
The business development office handles alliances for collaboration with companies, universities, and external research institutes. It is also involved in licensing intellectual property rights to companies in collaboration with RIKEN Innovation.
Mission of Translational Research Office (TRO), the competent team which consists of number of experts of translational research (TR) from industry, academic TR institutes, regulatory organizations, is to support projects establishing clinical development plan.
