Multi-Target Drug Design Approaches for Multifactorial Diseases: From Neurodegenerative to Cardiovascular Applications

2014 ◽  
Vol 21 (24) ◽  
pp. 2743-2787 ◽  
Author(s):  
M.G. Katselou ◽  
A.N. Matralis ◽  
A.P. Kourounakis
Keyword(s):  
Drug Design ◽  
Multifactorial Diseases ◽  
Target Drug

Molecular Modeling Techniques Applied to the Design of Multitarget Drugs: Methods and Applications

2021 ◽  
Vol 21 ◽  
Author(s):  
Larissa Henriques Evangelista Castro ◽  
Carlos Mauricio R. Sant'Anna
Keyword(s):  
Drug Design ◽  
Similar Efficacy ◽  
Learning Approaches ◽  
Resistance Development ◽  
Multifactorial Diseases ◽  
Target Drug ◽  
Single Target ◽  
Modeling Techniques ◽  
Computer Based ◽  
New Challenges

: Multifactorial diseases, such as cancer and diabetes present a challenge for the traditional “one-target, one disease” paradigm due to their complex pathogenic mechanisms. Although a combination of drugs can be used, a multitarget drug may be a better choice face of its efficacy, lower adverse effects and lower chance of resistance development. The computer-based design of these multitarget drugs can explore the same techniques used for single-target drug design, but the difficulties associated to the obtention of drugs that are capable of modulating two or more targets with similar efficacy impose new challenges, whose solutions involve the adaptation of known techniques and also to the development of new ones, including machine-learning approaches. In this review, some SBDD and LBDD techniques for the multitarget drug design are discussed, together with some cases where the application of such techniques led to effective multitarget ligands.

From in silico target prediction to multi-target drug design: Current databases, methods and applications

2011 ◽  
Vol 74 (12) ◽  
pp. 2554-2574 ◽  
Author(s):  
Alexios Koutsoukas ◽  
Benjamin Simms ◽  
Johannes Kirchmair ◽  
Peter J. Bond ◽  
Alan V. Whitmore ◽  
...  
Keyword(s):  
Drug Design ◽  
In Silico ◽  
Target Prediction ◽  
Target Drug

The Use of Stilbene Scaffold in Medicinal Chemistry and Multi- Target Drug Design

2016 ◽  
Vol 23 (23) ◽  
pp. 2439-2489 ◽  
Author(s):  
Elisa Giacomini ◽  
Sebastiano Rupiani ◽  
Laura Guidotti ◽  
Maurizio Recanatini ◽  
Marinella Roberti
Keyword(s):  
Drug Design ◽  
Medicinal Chemistry ◽  
Target Drug

scholarly journals Systematic assessment of fragment identification for multi‐target drug design

ChemMedChem ◽  
2020 ◽  
Author(s):  
Steffen Brunst ◽  
Jan S. Kramer ◽  
Whitney Kilu ◽  
Jan Heering ◽  
Julius Pollinger ◽  
...  
Keyword(s):  
Drug Design ◽  
Systematic Assessment ◽  
Target Drug

scholarly journals Evolution of kinase polypharmacology across HSP90 drug discovery

2020 ◽  
Author(s):  
Albert A. Antolin ◽  
Paul A. Clarke ◽  
Ian Collins ◽  
Paul Workman ◽  
Bissan Al-Lazikani
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
Small Molecules ◽  
Protein Kinases ◽  
Experimental Methods ◽  
Experimental Characterization ◽  
Hsp90 Inhibitors ◽  
Target Drug ◽  
Clinical Candidate

AbstractMost small molecules interact with several target proteins but this polypharmacology is seldom comprehensively investigated or explicitly exploited during drug discovery. Here, we use computational and experimental methods to systematically characterize the kinase cross-pharmacology of representative HSP90 inhibitors. We demonstrate that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, display unique off-target kinase pharmacology as compared to other HSP90 inhibitors. We also demonstrate that polypharmacology evolved during the optimisation to discover luminespib and that the hit, leads and clinical candidate all have different polypharmacological profiles. We conclude that the submicromolar target inhibition of protein kinases by ganetespib may have potential clinical significance and we recommend the computational and experimental characterization of polypharmacology earlier in drug discovery projects to unlock new multi-target drug design opportunities.

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