Illuminating the Druggable Genome

Work led by Tudor Oprea at UNM has been published in Nature Reviews Drug Discovery. This work describes some of the background and motivation behind the NIH Illuminating the Druggable Genome effort we are funded by to investigate the dark kinome.

Abstract: A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately two out of five proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.

Oprea TI, Bologa CG, Brunak S, Campbell A, Gan G, Gaulton A, Gomez SM, Guha R, Hersey A, Holmes J, Jadhav A, Jensen LJ, Johnson GL, Karlson A, Leach AR, Ma’ayan A, Malovannaya A, Mani S, Mathias SL, McManus M, Meehan T, von Mering C, Muthas D, Nguyen DC, Overington JP, Papadatos G, Qin J, Reich C, Roth BL, Schürer SC, Simeonov A, Sklar LA, Simeonov A, Southall N, Tomita S, Tudose I, Ursu O, Vidović D, Waller A, Westergaard S, Yang JJ, Zahoranszky-Kohalmi G. Unexplored Therapeutic Opportunities in the Human Genome. Nat. Rev.Drug Discov. 2018. Feb 23 https://doi.org/10.1038/nrd.2018.14.