Computational and Practical Aspects of Drug Repositioning

被引:73
作者
Oprea, Tudor I. [1 ]
Overington, John P. [2 ]
机构
[1] Univ New Mexico, Sch Med, Dept Internal Med, Translat Informat Div, Albuquerque, NM 87131 USA
[2] European Mol Biol Lab, European Bioinformat Inst, Hinxton CB10 1SD, England
关键词
PHARMACOLOGY; SCREEN;
D O I
10.1089/adt.2015.29011.tiodrrr
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The concept of the hypothesis-driven or observational-based expansion of the therapeutic application of drugs is very seductive. This is due to a number of factors, such as lower cost of development, higher probability of success, near-term clinical potential, patient and societal benefit, and also the ability to apply the approach to rare, orphan, and underresearched diseases. Another highly attractive aspect is that the "barrier to entry" is low, at least in comparison to a full drug discovery operation. The availability of high-performance computing, and databases of various forms have also enhanced the ability to pose reasonable and testable hypotheses for drug repurposing, rescue, and repositioning. In this article we discuss several factors that are currently underdeveloped, or could benefit from clearer definition in articles presenting such work. We propose a classification scheme-drug repositioning evidence level (DREL)-for all drug repositioning projects, according to the level of scientific evidence. DREL ranges from zero, which refers to predictions that lack any experimental support, to four, which refers to drugs approved for the new indication. We also present a set of simple concepts that can allow rapid and effective filtering of hypotheses, leading to a focus on those that are most likely to lead to practical safe applications of an existing drug. Some promising repurposing leads for malaria (DREL-1) and amoebic dysentery (DREL-2) are discussed.
引用
收藏
页码:299 / 306
页数:8
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