Identifying New Drug Targets by Illuminating the Druggable Genome

Abstract

Results from the Human Genome Project have revealed that the human genome contains ~20,000 genes. Of these, ~4,500 genes are considered part of the “druggable genome,” defined as the subset of the human genome that expresses proteins that are able to bind drug-like molecules. However, existing clinical drugs only target a few hundred of these proteins, leaving a subset of ~4000 proteins within this druggable genome that still remain largely understudied. Three protein families, the ion channels, G-protein-coupled receptors, and protein kinases, have been identified to contain adequate numbers of understudied members and are well-established druggable families with high potential to impact human health once disease associations are made. Further investigation is warranted to discover crucial knowledge about the function of understudied members of these protein families and to elucidate their roles in health and disease. To improve our scientific understanding of understudied members of these three protein families, the National Institutes of Health (NIH) Common Fund launched the Illuminating the Druggable Genome (IDG) Program in 2014. The overall goal of the IDG Program is to catalyze research in areas of biology that are currently understudied but that have high potential to impact human health by (1) identifying biochemical, cellular, or animal model phenotypes for understudied proteins from druggable gene families, (2) enabling further investigation of those proteins by providing reagents and tools, and (3) generating, maintaining, and facilitating the use of a minable knowledge base. A key resource from this program, Pharos (https://pharos.nih.gov/idg/index), aggregates protein information from several sources, allowing researchers easy access to in depth protein data, enabling them to enhance their research and help identify new targets of interest. In addition, the IDG program works to develop molecular probes (small molecules), molecular tools and assays, transgenic mice, recombinant cell lines, data, and digital resources for 100+ orphan GPCRs, ion channels and kinases. These resources are now available for use by the scientific community, with the IDG Program continuing to build on the knowledge and tools developed and generate, aggregate, analyze, and disseminate knowledge and tools around understudied proteins. These new knowledge and tool sets are intended to equip the scientific community, including small businesses and the pharmaceutical industry, with the ability to explore previously understudied biology with the potential to rapidly impact human health. It is hoped that the resources developed, and the discoveries made by the IDG Program, will enable the advancement of new treatments and diagnostics in order to get more treatments to more patients more quickly.