Ignite Academic Theater Presentation

Identifying New Drug Targets by Illuminating the Druggable Genome

• AP

  Aaron Pawlyk, PhD

  Senior Advisor
  National Institutes of Health

Background. Of the approximately 20,000 protein-coding genes in the human genome, few have been studied intensively. Approximately 3,000 proteins are estimated to be part of the “druggable genome,” the subset of genes encoding proteins with the ability to bind drug-like molecules. Yet, less than ten percent of druggable proteins are currently targeted by FDA-approved drugs due to inherent difficulties tackling understudied and unknown targets. This lack of attention to most of the proteome persists, despite evidence that understudied proteins are often both interesting and important in biological processes. To address this gap, the NIH Common Fund launched a three-year pilot program in 2014, Illuminating the Druggable Genome (IDG). Following the success of this pilot, the NIH funded an IDG implementation phase in 2017. During the remaining six-years, the IDG program aims to identify novel drug targets, with a focus on understudied members of three gene families: the non-olfactory G-protein coupled receptors, protein kinases, and ion channels.

Resources. Information about proteins encoded by the druggable genome is concentrated in a central location, Pharos (https://pharos.nih.gov/idg/index) and a suite of medium-to-high throughput methods are being applied to understudied proteins across experimental systems from the molecular level to living organisms, some already available to the greater biomedical research community (https://commonfund.nih.gov/idg/programresources). Currently, the IDG program will extend the ability to aggregate, analyze, and visualize data on the understudied proteome as well as generate small molecule tools, DNA-based reagents, cell and mouse lines, and novel data around the understudied ion channels, GPCRs, and protein kinases.

Collaborative Opportunities. The data and resources generated by the IDG will be made available to the research community. To maximize impact, the IDG program will seek broad input and partnerships with the biomedical research community and, pending availability of future funds, the NIH intends to release future funding opportunity announcements to facilitate these interactions and the uptake of data and reagents.

Summary. The IDG program seeks to identify novel drug targets and further scientific research by shedding light on a subset of genes and proteins for which little publicly available information or active research exists. Through collaborations and spin-off projects, proof-of-concept studies will determine the relevance of potential therapeutic targets to human health and disease. The long-term effect of the IDG program and its collaborative partners will be expansion of the potential therapeutic space, providing an impetus for more efficient, disease-specific, investigations and the ability to more effectively address unmet medical needs.