eRepo-ORP: Exploring the Opportunity Space to Combat Orphan Diseases with Existing Drugs |
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| Authors: | Michal Brylinski Misagh Naderi Rajiv Gandhi Govindaraj Jeffrey Lemoine |
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| Institution: | 1. Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA;2. Center for Computation & Technology, Louisiana State University, Baton Rouge, LA 70803, USA;3. Division of Computer Science and Engineering, Louisiana State University, Baton Rouge, LA 70803, USA |
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| Abstract: | 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/. |
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| Keywords: | FDA Food and Drug Administration GDT Global Distance Test KRAS GTPase KRas PDB Protein Data Bank PTK6 protein-tyrosine kinase 6 RALD Ras-associated autoimmune leukoproliferative disorder TC Tanimoto coefficient TM score Template Modeling score drug repositioning drug repurposing orphan diseases rare diseases DrugBank |
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