+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Identification of drug candidates and repurposing opportunities through compound-target interaction networks



Identification of drug candidates and repurposing opportunities through compound-target interaction networks



Expert Opinion on Drug Discovery 10(12): 1333-1345



System-wide identification of both on- and off-targets of chemical probes provides improved understanding of their therapeutic potential and possible adverse effects, thereby accelerating and de-risking drug discovery process. Given the high costs of experimental profiling of the complete target space of drug-like compounds, computational models offer systematic means for guiding these mapping efforts. These models suggest the most potent interactions for further experimental or pre-clinical evaluation both in cell line models and in patient-derived material. The authors focus here on network-based machine learning models and their use in the prediction of novel compound-target interactions both in target-based and phenotype-based drug discovery applications. While currently being used mainly in complementing the experimentally mapped compound-target networks for drug repurposing applications, such as extending the target space of already approved drugs, these network pharmacology approaches may also suggest completely unexpected and novel investigational probes for drug development. Although the studies reviewed here have already demonstrated that network-centric modeling approaches have the potential to identify candidate compounds and selective targets in disease networks, many challenges still remain. In particular, these challenges include how to incorporate the cellular context and genetic background into the disease networks to enable more stratified and selective target predictions, as well as how to make the prediction models more realistic for the practical drug discovery and therapeutic applications.

(PDF emailed within 0-6 h: $19.90)

Accession: 058039146

Download citation: RISBibTeXText

PMID: 26429153

DOI: 10.1517/17460441.2015.1096926


Related references

Interactive visual analysis of drug-target interaction networks using Drug Target Profiler, with applications to precision medicine and drug repurposing. Briefings in Bioinformatics 2018, 2018

Using compound similarity and functional domain composition for prediction of drug-target interaction networks. Medicinal Chemistry ) 6(6): 388-395, 2011

Using Compound Similarity and Functional Domain Composition for Prediction of Drug-Target Interaction Networks. Medicinal Chemistry 6(6): 388-395, 2010

Identification of drug repurposing candidates based on a miRNA-mediated drug and pathway network for cardiac hypertrophy and acute myocardial infarction. Human Genomics 12(1): 52, 2018

A Drug Repurposing Method Based on Drug-Drug Interaction Networks and Using Energy Model Layouts. Methods in Molecular Biology 1903: 185-201, 2018

The Mu.Ta.Lig. Chemotheca: A Community-Populated Molecular Database for Multi-Target Ligands Identification and Compound-Repurposing. Frontiers in Chemistry 6: 130, 2018

Identification of chemogenomic features from drug-target interaction networks using interpretable classifiers. Bioinformatics 28(18): I487-I494, 2013

The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing. European Journal of Medicinal Chemistry 62: 777-784, 2013

Identification of drug target candidates of the swine pathogen Actinobacillus pleuropneumoniae by construction of protein-protein interaction network. Genes and Genomics 40(8): 847-856, 2018

The topology of drug-target interaction networks: implicit dependence on drug properties and target families. Molecular Biosystems 5(9): 1051-1057, 2009

A Comparative Study of Cluster Detection Algorithms in Protein-Protein Interaction for Drug Target Discovery and Drug Repurposing. Frontiers in Pharmacology 10: 109, 2019

Drug Repurposing by Simulating Flow Through Protein-Protein Interaction Networks. Clinical Pharmacology and Therapeutics 103(3): 511-520, 2017

Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing. Plos Computational Biology 12(10): E1005135, 2017

New drug candidates for treatment of atypical meningiomas: An integrated approach using gene expression signatures for drug repurposing. Plos One 13(3): E0194701, 2018

Construction of an miRNA-regulated drug-pathway network reveals drug repurposing candidates for myasthenia gravis. International Journal of Molecular Medicine 39(2): 268-278, 2017