Drug Repositioning in Inflammatory Bowel Disease Based on Genetic Information

被引:12
作者
Collij, Valerie [1 ]
Festen, Eleonora A. M. [1 ]
Alberts, Rudi [1 ]
Weersma, Rinse K. [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, POB 30001, NL-9700 RB Groningen, Netherlands
关键词
candidate genes; drug identification; drug repositioning; inflammatory bowel disease; Crohn's disease; ulcerative colitis; GENOME-WIDE ASSOCIATION; ULCERATIVE-COLITIS; SUSCEPTIBILITY LOCI; CROHNS-DISEASE; PATHOGENESIS; TOFACITINIB;
D O I
10.1097/MIB.0000000000000912
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background:Currently, 200 genetic risk loci have been identified for inflammatory bowel disease (IBD). Although these findings have significantly advanced our insight into IBD biology, there has been little progress in translating this knowledge toward clinical practice, like more cost-efficient drug development. Our aim was to use genetic knowledge to identify drugs that warrant further investigation in IBD treatment.Methods:We hypothesized that proteins encoded by IBD candidate genes are potential IBD drug targets because genetic information can increase successful drug identification. We identified drugs that target the proteins encoded by IBD candidate genes using the DrugBank. We included proteins that are in direct protein-protein interaction with proteins encoded by IBD risk genes. Promising potential IBD drugs were selected based on a manual literature search of all identified drugs (PubMed, ClinicalTrials.gov).Results:We have identified 113 drugs that could potentially be used in IBD treatment. Fourteen are known IBD drugs, 48 drugs have been, or are being investigated in IBD, 19 are being used or being investigated in other inflammatory disorders treatment, and 32 are investigational new drugs that have not yet been registered for clinical use.Conclusions:We confirm that proteins encoded by IBD candidate genes are targeted by approved IBD therapies. Furthermore, we show that Food and Drug Administration-approved drugs could possibly be repositioned for IBD treatment. We also identify investigational new drugs that warrant further investigation for IBD treatment. Incorporating this process in IBD drug development will improve the utilization of genetic data and could lead to the improvement of IBD treatment.
引用
收藏
页码:2562 / 2570
页数:9
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