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Drug Repurposing from an Academic Perspective.

Division of Biocomputing, Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, MSC11 6145, Albuquerque, NM 87131, USA.
Drug Discovery Today Therapeutic Strategies 12/2011; 8(3-4):61-69. DOI: 10.1016/j.ddstr.2011.10.002
Source: PubMed

ABSTRACT Academia and small business research units are poised to play an increasing role in drug discovery, with drug repurposing as one of the major areas of activity. Here we summarize project status for a number of drugs or classes of drugs: raltegravir, cyclobenzaprine, benzbromarone, mometasone furoate, astemizole, R-naproxen, ketorolac, tolfenamic acid, phenothiazines, methylergonovine maleate and beta-adrenergic receptor drugs, respectively. Based on this multi-year, multi-project experience we discuss strengths and weaknesses of academic-based drug repurposing research. Translational, target and disease foci are strategic advantages fostered by close proximity and frequent interactions between basic and clinical scientists, which often result in discovering new modes of action for approved drugs. On the other hand, lack of integration with pharmaceutical sciences and toxicology, lack of appropriate intellectual coverage and issues related to dosing and safety may lead to significant drawbacks. The development of a more streamlined regulatory process world-wide, and the development of pre-competitive knowledge transfer systems such as a global healthcare database focused on regulatory and scientific information for drugs world-wide, are among the ideas proposed to improve the process of academic drug discovery and repurposing, and to overcome the "valley of death" by bridging basic to clinical sciences.

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Available from: Stuart S Winter, Aug 11, 2015
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    • "Drug repositioning is highly attractive in that it partly focuses on drugs with regulatory-approved clinical safety data, and there are thousands of regulatory-approved biologically-active drugs already available. If these approved drugs include agents with efficacy in the treatment of PD progression, repositioning may represent a more efficient process [1] [2] [3] [4] [5] [6] [7] [8] than original drug discovery [9]. Indeed, repositioning in some therapeutic areas has provided crucial strategic advances in the introduction of new treatments (e.g. "
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    • "Recently, the use of drug repurposing as a key strategy within academia and public research institutes has been extensively discussed [87] [88] [89]. Public institutions, including public research laboratories and universities, have contributed to the development of nearly 90% of new indications for previously approved drugs [88]. "
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    ABSTRACT: Drug repurposing/reprofiling has attracted considerable attention during the last decade. The object of such approach is to discover second or further medical uses of known chemicals, i. e. targeting existing, withdrawn or abandoned drugs, or yet to be pursued clinical candidates to new disease areas. Recently (2011-2012), the US and UK governments launched public-private joint initiatives towards finding new uses of previously shelved compounds (drug rescue). While in the past repurposing emerged from serendipitous findings and/or from rational exploitation of drug side-effects (e.g. sildenafil, aspirin), the current tendency in the drug development field focuses on knowledge-based drug repurposing, particularly, computer-aided repositioning approaches. The present chapter reviews different cheminformatic and bioinformatic applications, as well as high-throughput literature analysis, oriented to the discovery of new medical uses of known drugs. Applications of such strategies to the discovery of innovative medications for neglected or rare diseases are discussed. Finally, we also review publicly available resources (e.g. chemical libraries) valuable for reprofiling.
    Frontiers in Computational Chemistry (Vol. 1), Edited by Zaheer-ul-Haq, J. D. Madura, 01/2015: chapter 2: pages 44-81; Bentham Science., ISBN: 978-1-60805-865-5
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    • "Among these compounds, 197 of US Illicit drugs are included. We also incorporate the CNS drugs reported in the DrugBank database and the PubChem library for later study of polypharmacology and drug repurposing (Ashburn and Thor, 2004; Oprea et al., 2011). • DA Pathways (current: 594 records): The corresponding signaling pathways for DA proteins have been mapped through public databases, such as KEGG (Kanehisa and Goto, 2000; Kanehisa et al., 2012) and DrugBank (Wishart et al., 2006, 2008; Knox et al., 2011) using our established data mining analysis tools. "
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    ABSTRACT: Drug abuse (DA) and addiction is a complex illness, broadly viewed as a neurobiological impairment with genetic and environmental factors that influence its development and manifestation. Abused substances can disrupt the activity of neurons by interacting with many proteins, particularly G-protein coupled receptors (GPCRs). A few medicines that target the central nervous system (CNS) can also modulate DA related proteins, such as GPCRs, which can act in conjunction with the controlled psychoactive substance(s) and increase side effects. To fully explore the molecular interaction networks that underlie DA and to effectively modulate the GPCRs in these networks with small molecules for DA treatment, we built a drug-abuse domain specific chemogenomics knowledgebase (DA-KB) to centralize the reported chemogenomics research information related to DA and CNS disorders in an effort to benefit researchers across a broad range of disciplines. We then focus on the analysis of GPCRs as many of them are closely related with DA. Their distribution in human tissues was also analyzed for the study of side effects caused by abused drugs. We further implement our computational algorithms/tools to explore DA targets, DA mechanisms and pathways involved in polydrug addiction and to explore polypharmacological effects of the GPCR ligands. Finally, the polypharmacology effects of GPCRs-targeted medicines for DA treatment were investigated and such effects can be exploited for the development of drugs with polypharmacophore for DA intervention. The chemogenomics database and the analysis tools will help us better understand the mechanism of drugs abuse and facilitate to design new medications for system pharmacotherapy of DA.
    Frontiers in Pharmacology 02/2014; 5:3. DOI:10.3389/fphar.2014.00003 · 3.80 Impact Factor
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