Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jan 17;7(1):3.
doi: 10.1186/s40169-017-0181-2.

A perspective on multi-target drug discovery and design for complex diseases

Rona R Ramsay  1 , Marija R Popovic-Nikolic  2 , Katarina Nikolic  2 , Elisa Uliassi  3 , Maria Laura Bolognesi  3
Affiliations

A perspective on multi-target drug discovery and design for complex diseases

Rona R Ramsay et al. Clin Transl Med. .

Abstract

Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets. This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.

Keywords: Biological assays; Cancer; Cheminformatics; Multi-target drugs; Neurodegeneration; Virtual screening.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Distribution of the new molecular entities (NMEs) approved from 2015 to 2017 (status September 2017), organized according to the different classes of NMEs
Fig. 2
Fig. 2
The 21 multi-target drugs and 10 therapeutic combinations approved in 2015–2017 organized according to their Anatomical Therapeutic Chemical (ATC) Classification System
Fig. 3
Fig. 3
Rational design of multi-target compounds
Fig. 4
Fig. 4
Schematic representation of the QSAR workflow
See this image and copyright information in PMC

References

    1. Bolognesi ML. Polypharmacology in a single drug: multitarget drugs. Curr Med Chem. 2013;20(13):1639–1645. doi: 10.2174/0929867311320130004. - DOI - PubMed
    1. Bolognesi ML, Cavalli A. Multitarget drug discovery and polypharmacology. ChemMedChem. 2016;11(12):1190–1192. doi: 10.1002/cmdc.201600161. - DOI - PubMed
    1. Morphy R, Kay C, Rankovic Z. From magic bullets to designed multiple ligands. Drug Discov Today. 2004;9(15):641–651. doi: 10.1016/S1359-6446(04)03163-0. - DOI - PubMed
    1. Youdim MBH, Buccafusco JJ. Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders. Trends Pharm Sci. 2005;26(1):27–35. doi: 10.1016/j.tips.2004.11.007. - DOI - PubMed
    1. Roth BL, Sheffler DJ, Kroeze WK. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat Rev Drug Discov. 2004;3(4):353–359. doi: 10.1038/nrd1346. - DOI - PubMed