Journal of Molecular Biology, Volume 430, 20 July 2018,
About 7000 rare, or orphan, diseases affect more than 350 million people worldwide. Although these conditions collectively pose significant health care problems, drug companies seldom develop drugs for orphan diseases due to extremely limited individual markets. Consequently, developing new treatments for often life-threatening orphan diseases is primarily contingent on financial incentives from governments, special research grants, and private philanthropy. Computer-aided drug repositioning is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Here, we present eRepo-ORP, a comprehensive resource constructed by a large-scale repositioning of existing drugs to orphan diseases with a collection of structural bioinformatics tools, including eThread, eFindSite, and eMatchSite. Specifically, a systematic exploration of 320,856 possible links between known drugs in DrugBank and orphan proteins obtained from Orphanet reveals as many as 18,145 candidates for repurposing. In order to illustrate how potential therapeutics for rare diseases can be identified with eRepo-ORP, we discuss the repositioning of a kinase inhibitor for Ras-associated autoimmune leukoproliferative disease. The eRepo-ORP data set is available through the Open Science Framework at https://osf.io/qdjup/.
Antagonists And Inhibitors; Article; Autoimmune Disease; Autoimmune Lymphoproliferative Syndrome; Biology; Computational Biology; Drug Database; Drug Development; Drug Discovery; Drug Identification; Drug Repositioning; Drug Repurposing; Drug Targeting; DrugBank; Economics; Food And Drug Administration; Human; Humans; Internet; Metabolism; Orphan Disease; Orphan Diseases; Phosphotransferase Inhibitor; Priority Journal; Procedures; Protein Kinase Inhibitor; Protein Kinase Inhibitors; Protein Structure; Rare Disease; Rare Diseases; Ras Associated Autoimmune Leukoproliferative Disease; Ras Protein; Ras Proteins; Reproducibility; Reproducibility Of Results; Statistics And Numerical Data; Structural Bioinformatics; Vandetanib; Global