RIKEN

Approach to Selecting Drug Discovery Themes and Projects

　For the Drug Discovery and Medical Technology Platforms, we have established the six guidelines (standards) shown below concerning the selection of topics targeted for support by the drug discovery themes and projects within RIKEN and elsewhere. Formulating these standards is positioned as part of the drug discovery exit strategy. At the start of the research, they have been established to facilitate the focus and selection of topics of significance for academic research with high potential for successful drug discovery research.

　The table below outlines the details of the assessment.

Assessment and Methods of Selection Based on the Selection Guidelines

1. Is it an area of disease where RIKEN should be engaged?
Categorizing areas of disease for drug discovery themes and drug discovery classification, we prioritize drugs for treating epidemics in developing countries (neglected diseases), drugs for treating diseases where the number of patients is few (orphan drugs) and areas of disease with low levels of treatment satisfaction and no effective drugs. (The red areas in the diagram below indicate strong areas. Click here for more details.) We also give preference to the selection of innovative drug discovery and medical technology based on new concepts capable of capitalizing on the results of basic research by RIKEN and academic research institutions.

2. Novelty and reliability of the mechanism (CIM)
The mechanism for drug discovery themes requires the compatibility of two contradictory items: novelty (drug discovery data based on unprecedented new molecular mechanisms) and reliability (referred to as confidence in mechanism, abbreviated CIM. In the drug discovery field, this indicates confidence that the molecular mechanism of the target is linked to the actual treatment due to drug efficacy in knockout animals, siRNA or disease animal models.). We collect and evaluate information based on published and unpublished data by the proposing laboratory as well as a diligent examination of the literature.

3. Potential for investigating promising candidates for drugs
Even when the target presents some novelty and the therapy is sufficiently reliable, it is not possible to reach the patient if tying in with actual “pharmaceuticals” proves difficult. Even in cases that are difficult under normal conditions, there are cases where the basic technologies of RIKEN can turn the impossible into the possible. If it is a question of low molecular targets, we investigate in great detail whether the structure is already understood through x-rays or NMR, whether structural analysis is possible at RIKEN, and whether or not the structure of the target has binding sites where low molecules can be strongly bound (see diagram below). With respect to antibody drugs, nucleic acid drugs and cell therapies, we determine the order of preference by assessing whether or not the targets and areas of disease are ones where the sophisticated RIKEN technologies can be put to practical use.

4. Presence or absence of prior drugs and differentiation
It is preferable that the targets for involvement are completely new targets with no prior drugs, but in case of prior drugs, we investigate what stage they are at and their weaknesses. In the Drug Discovery and Medical Technology Platforms, we have put together a system capable of searching several millions of entries in inhibitor databases such as the Thomson Reuters database and ChEMBL for prior drugs, and if there is a prior drug, to analyze the potential for differentiation.

5. Is there already some progress in the stages of the research?
Another important topic for investigation is to what degree there has been progress in the stages of a previously identified chemical compound from the perspective of drug discovery themes. Our program divides the stages into three classes: the S (seed) stage, the L (lead) stage and the P (clinical) stage with further subdivisions for each stage of S0 to S3, L1 to L3 and P0 to P3. Please see here for definitions. The theme extends from the S1 to the L2 stages, which is the investigative stage before we narrow down the candidate compounds to one or a small number. This is when the theme leader and portfolio manager (the portfolio manager is responsible for several themes) work together to drive drug discovery. The project refers to the L3 stage and beyond, which is the development stage for the candidate compound when we assign a project leader to push hard for development. In order to judge these stages, the program collaborates with internal and external partners to ready a structure for pharmacological testing of drug efficacy and all types of ADMET testing in addition to activity toward the target.

Please see below for definitions of each stage.
S0:Identify the target
S1:Construct screening systems and undertake screening
S2:Find a hit compound and develop seeds
S3:Find a promising drug discovery seed and develop leads
L1:Find responsive lead compounds as a result of animal testing, optimization
L2:Identify several promising compounds, optimization in order to progress to GLP testing
L3:Select P0 candidate compounds as a result of non GLP testing
P0:Select candidate compounds as a result of GLP testing
P1/P2/P3:Correspond to Ph I/II/ III of clinical testing

With respect to the important stages among the above, we make detailed decisions on the definitions for moving up to the next stage. (Click here for details.)

6. Does the proponent have the enthusiasm and time to actively push for drug discovery?
In drug discovery, it is essential that researchers from many specialist fields collaborate closely while pushing tenaciously forward. It is also essential to administer the themes by assessing successive outcome of the test data in a timely manner. Therefore, the theme proponent is interviewed by the coordinator and the portfolio manager while polishing the proposals together. When making decisions about which themes to push, we also take into account whether or not all proponents have the enthusiasm and sufficient research time to spend on drug discovery.

Order of Preference for Themes

→B and above are the focus themes
→We refer to assessment ratings and aggregate results to determine final order of preference 

Standards for progressing to the next stage

Please contact us for consultation

There are many topics that must be clarified before implementing drug discovery. (Please refer to the diagram below.) We have taken these topics into account when establishing the guidelines. Our program is staffed with specialists in drug discovery together with researchers who are knowledgeable about sophisticated drug discovery technologies. We have put in place a structure capable of promoting drug discovery themes and drug discovery projects for everyone. Do be sure to consult with us.