Computational Predictions for Multi-Target Drug Design

2018 ◽  
pp. 27-50 ◽  
Author(s):  
Neelima Gupta ◽  
Prateek Pandya ◽  
Seema Verma
Keyword(s):  
Drug Design ◽  
Target Drug ◽  
Computational Predictions

Computer Aided Drug Design for Multi-Target Drug Design: SAR /QSAR, Molecular Docking and Pharmacophore Methods

2017 ◽  
Vol 18 (5) ◽  
pp. 556-575 ◽  
Author(s):  
Azizeh Abdolmaleki ◽  
Jahan Ghasemi ◽  
Fatemeh Ghasemi
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Computer Aided Drug Design ◽  
Target Drug ◽  
Computer Aided

The Neurodegenerative Characteristics of Alzheimer’s Disease and Related Multi-Target Drug Design Studies

2019 ◽  
pp. 473-504
Author(s):  
Hayrettin Ozan Gülcan ◽  
Ilkay Erdogan Orhan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Design ◽  
Design Studies ◽  
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

Knowledgebase for addiction-related genes: Is it possible an extrapolation to rational multi-target drug design?

2008 ◽  
Vol 16 (20) ◽  
pp. 9346-9348 ◽  
Author(s):  
L. Michel Espinoza-Fonseca
Keyword(s):  
Drug Design ◽  
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

The Multi-Target Drug Design Era is Here, Consider it

2012 ◽  
Vol 1 (1) ◽  
Author(s):  
Donald Sikazwe
Keyword(s):  
Drug Design ◽  
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.

scholarly journals GSK-3β, FYN, and DYRK1A: Master Regulators in Neurodegenerative Pathways

2021 ◽  
Vol 22 (16) ◽  
pp. 9098
Author(s):  
Stefania Demuro ◽  
Rita M. C. Di Martino ◽  
Jose A. Ortega ◽  
Andrea Cavalli
Keyword(s):  
Drug Design ◽  
Neuromuscular Disorders ◽  
Computer Assisted ◽  
Design Strategies ◽  
Medical Needs ◽  
Target Drug ◽  
Functional Aspects ◽  
Disease Modifying Agents ◽  
Gsk 3Β ◽  
Unmet Medical Needs

Protein kinases (PKs) have been recognized as central nervous system (CNS)-disease-relevant targets due to their master regulatory role in different signal transduction cascades in the neuroscience space. Among them, GSK-3β, FYN, and DYRK1A play a crucial role in the neurodegeneration context, and the deregulation of all three PKs has been linked to different CNS disorders with unmet medical needs, including Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal lobar degeneration (FTLD), and several neuromuscular disorders. The multifactorial nature of these diseases, along with the failure of many advanced CNS clinical trials, and the lengthy approval process of a novel CNS drug have strongly limited the CNS drug discovery. However, in the near-decade from 2010 to 2020, several computer-assisted drug design strategies have been combined with synthetic efforts to develop potent and selective GSK-3β, FYN, and DYRK1A inhibitors as disease-modifying agents. In this review, we described both structural and functional aspects of GSK-3β, FYN, and DYRK1A and their involvement and crosstalk in different CNS pathological signaling pathways. Moreover, we outlined attractive medicinal chemistry approaches including multi-target drug design strategies applied to overcome some limitations of known PKs inhibitors and discover improved modulators with suitable blood–brain barrier (BBB) permeability and drug-like properties.

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