The National Institutes of Health’s Illuminating the Druggable Genome (IDG) program generated an extensive array of resources to catalyze research on new drug targets. The databases and tools developed by the program, which expands the scientific community’s ability to explore understudied biology, were described in a series of articles published in Drug Discovery Today.
The NIH Common Fund launched IDG in 2014 to bolster research on proteins that have a high potential to serve as drug targets. The program developed resources to facilitate research on all human proteins (the human proteome) and on proteins that were understudied among three specific protein families, ion channels, G-protein-coupled receptors (GPCRs), and kinases, since many well-studied proteins from these families serve as drug targets.
A significant achievement of the IDG program was the development of two resources that broaden the ability of researchers to investigate the human proteome: the Target Central Resource Database (TCRD) and Pharos (a search portal). The TCRD integrates information on the human proteome from over 80 sources of data, while Pharos is a search interface that enables users to download and visualize data from the TCRD. These tools allow the scientific community to study the biological pathways in which proteins function and to visualize the relationships between diseases and potential drug targets.
An important feature included in the TCRD and Pharos is a classification system that categorizes proteins based on where they are in the drug development pipeline. The classification system has four levels with some proteins categorized as existing drug targets, some categorized as having high potential for drug development based on their ability to bind small molecules, others categorized as having well-known biological roles, and the rest categorized as largely unexplored. Providing these classifications to the scientific community can catalyze the discovery of drug targets by strategically directing researchers towards understudied proteins.
In addition to generating resources that facilitate research on the entire human proteome, the primary goal of IDG was to develop tools and resources specific to understudied proteins from the three protein families of interest. For GPCRs, IDG developed resources that expand the capacity of scientists to screen, identify, and synthesize small molecules (called probes) that can be used in further investigation of these understudied proteins. For kinases, the program developed a tool that quantifies kinases in cell lines and biopsy samples, a tool that defines the interaction networks of proteins near understudied kinases, and chemical tools for research on the functional consequences of inhibiting kinases. These and other kinase resources from the program shed light on the roles understudied kinases play in cells. For ion channels, IDG worked with another Common Fund program, the Knockout Mouse Phenotyping Program, to develop mouse models of understudied proteins from this family and identify their roles in human disease. The IDG program also developed an informatics tool that uses evolutionary information to predict functions of understudied ion channels and kinases.
The IDG program’s resources provide the scientific community with a diverse array of tools to investigate poorly characterized proteins that have the potential to lead to new drug targets for diseases and conditions that affect human health.
IDG is an NIH-wide effort managed collaboratively by the NIH Common Fund, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases.
