Drug Discovery Enhancement Project
Chemical Bank Platform
Support to Screen Drug-Lead Compounds by use of
Natural Product-based Chemical Library
Natural products are essential resources for drug discovery research because of the variety of their biological activity and chemical structures, but it is difficult to isolate many kinds of and large amounts of natural products.
In the chemical bank platform, we have established a natural products-based chemical library by collecting and storing secondary metabolites from microbes. Information on the compounds in the chemical library is recorded in the molecular database “NPEdia&rldquo; which is opened to the public on-line. In addition to natural compounds, “drugs in therapeutic use” are also collected in our chemical library as the basis for comparison to evaluate the activity of new compounds. To utilize the chemical library effectively, we facilitate the development of chemical array screening system, by which the interaction between the small molecules and proteins is detectable in trace amounts.
We support the identification of novel lead compounds and the optimization of chemical structures to promote drug discovery research, through development of technological platforms useful to enrich the chemical library and to advance the chemical array screening system.
Enrichment of the chemical bank “NPDepo” and chemical database “NPEdia”
In the chemical bank platform we constructed a chemical library consisting of a variety of natural products such as the secondary metabolites isolated from Actinomyces, fungi and plants. RIKEN Natural Products Depository (NPDepo) has collected and stored more than 24,000 compounds to date, with about 8,000 compounds available for research cooperation. We can also supply some of the chemicals to researchers who wish to use them for drug discovery research. The detailed information of compounds, such as name, compound IDs, structure, origins and bioactivity, are registered in the molecular database “NPEdia” and it is open to the public. In “NPEdia”, we can search for compounds with the terms above as query, and/or with sub-structures.
We are going to expand the number of compounds stored in “NPDepo” from 24,000 to 60,000, and also increase the number of distributable compounds from 8,000 to 20,000. We will also include more information in the chemical database “NPEdia”.
Fig.1 The chemical database “NPEdia” You can search for compounds by specifying keywords, partial structures, and the combination of them.
Support for drug discovery by chemical array-based screening
We fabricate chemical arrays carrying small molecules stored in “NPDepo”, and screen binders interacting with protein targets for drug discovery. The interaction between small molecules and a protein can be rapidly detected using the chemical array carrying more than 2,300 compounds per a chip. We construct and promote lead-exploring system by fabricating various chemical arrays.
An example of chemical array screening
We identified small molecules binding to carbonic anhydrase II (CAII), target protein for glaucoma treatment, by chemical array screening. The red spots shown in fig. 2A are hit spots detected on the array. These CAII-binding compounds have sulfonamide moiety (Fig. 2B).
Fig.2 Identification of CAII-binding compounds by chemical array screening.
