Two diseases, one approach: multitarget drug discovery in Alzheimer's and neglected tropical diseases

被引:74
作者
Prati, F. [1 ,2 ]
Uliassi, E. [2 ]
Bolognesi, M. L. [2 ]
机构
[1] Ist Italiano Tecnol, Dept Drug Discovery & Dev, I-16163 Genoa, Italy
[2] Univ Bologna, Dept Pharm & Biotechnol, I-40126 Bologna, Italy
关键词
TARGET-DIRECTED LIGANDS; SITE ACETYLCHOLINESTERASE INHIBITORS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BETA-AMYLOID FIBRILS; SYNTHETIC NAPHTHOQUINONES; MULTIFUNCTIONAL DRUGS; NETWORK PHARMACOLOGY; TRYPANOSOMA-CRUZI; BIVALENT LIGANDS; MULTIPLE LIGANDS;
D O I
10.1039/c4md00069b
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In the past decade, scientific advances in network pharmacology have laid the foundations for a polypharmacological approach to discover new drugs for complex diseases. There is now a comprehensive understanding that many incurable diseases are multifactorial in nature and, consequently, conventional drugs directed to a single molecular target are inadequate. To achieve a desired clinical outcome, a polypharmacological approach seeks to intervene in the diseased network using either combinations of multiple drugs or single small molecules modulating multiple targets. Both these approaches are equally feasible from a clinical standpoint. However, for various reasons which will be discussed in this review, the latter approach may be favoured for Alzheimer's disease (AD) and neglected tropical diseases (NTDs). With each passing year, an increasing number of multitarget drugs and drug candidates are being identified, and several proof-of-concepts for treating these two diseases have emerged. Herein, with an awareness of the obstacles and challenges faced, we explore small molecules that seek to modulate multiple targets with the ultimate goal of harnessing network pharmacology for therapeutic applications in AD and NTDs.
引用
收藏
页码:853 / 861
页数:9
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