+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Pharmacophore Modelling as a Virtual Screening Tool for the Discovery of Small Molecule Protein-protein Interaction Inhibitors

Pharmacophore Modelling as a Virtual Screening Tool for the Discovery of Small Molecule Protein-protein Interaction Inhibitors

Current Pharmaceutical Design 18(30): 4586-4598

Pharmacophore searches have become a popular tool for virtual screening of libraries to identify novel active substances that can be potentially developed into drugs. While they have been applied for years on common drug targets, their application in the discovery of protein-protein interaction inhibitors remains limited. This review describes current pharmacophore modelling methods applied in the discovery of novel inhibitors targeting protein-protein interactions. We first address the mimicry of protein-protein interactions with their respective inhibitors as observed in crystal structure complexes. This mimicry can be exploited to derive a pharmacophore query from protein-protein complex structures. We then discuss several cases where pharmacophore queries were utilized for the discovery of first-in-class inhibitors of their respective protein-protein interaction targets. These examples have demonstrated the usefulness of pharmacophore modelling in the quest for protein-protein interaction inhibitors.

Please choose payment method:

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

Accession: 036570851

Download citation: RISBibTeXText

DOI: 10.2174/138161212802651616

Related references

Pharmacophore-based virtual screening and biological evaluation of small molecule inhibitors for protein arginine methylation. Journal of Medicinal Chemistry 55(18): 7978-7987, 2012

AnchorQuery: Rapid online virtual screening for small-molecule protein-protein interaction inhibitors. Protein Science 27(1): 229-232, 2017

Protein Interface Pharmacophore Mapping Tools for Small Molecule Protein: Protein Interaction Inhibitor Discovery. Current Topics in Medicinal Chemistry 13(9): 989-1001, 2013

Protein interface pharmacophore mapping tools for small molecule protein: protein interaction inhibitor discovery. Current Topics in Medicinal Chemistry 13(9): 989-1001, 2014

Pharmacophore-based discovery of small-molecule inhibitors of protein-protein interactions between HIV-1 integrase and cellular cofactor LEDGF/p75. Chemmedchem 4(8): 1311-1316, 2009

Discovery of small molecule inhibitors of the PH domain leucine-rich repeat protein phosphatase (PHLPP) by chemical and virtual screening. Journal of Medicinal Chemistry 53(19): 6899-6911, 2010

Discovery of a Small-Molecule Inhibitor of Interleukin 15: Pharmacophore-Based Virtual Screening and Hit Optimization. Journal of Medicinal Chemistry 60(14): 6249-6272, 2017

Virtual screening and experimental validation reveal novel small-molecule inhibitors of 14-3-3 protein-protein interactions. Chemical Communications 49(76): 8468-8470, 2014

Immunosuppressive small molecule discovered by structure-based virtual screening for inhibitors of protein-protein interactions. Angewandte Chemie 51(1): 258-261, 2012

Ultra-High-Throughput Structure-Based Virtual Screening for Small-Molecule Inhibitors of Protein-Protein Interactions. Journal of Chemical Information and Modeling 56(2): 399-411, 2016

Discovery of potential pancreatic cholesterol esterase inhibitors using pharmacophore modelling, virtual screening, and optimization studies. Journal of Enzyme Inhibition and Medicinal Chemistry 26(4): 535-545, 2011

Discovery of new Phosphoinositide 3-kinase delta (PI3Kδ) inhibitors via virtual screening using crystallography-derived pharmacophore modelling and QSAR analysis. Medicinal Chemistry 2019, 2019

Virtual Screening with Structure-based Pharmacophore Model to Identify Small-molecule Inhibitors of CARM1. Journal of Chemical Information and Modeling 2019, 2019

Structure-based virtual screening toward the discovery of novel inhibitors for impeding the protein-protein interaction between HIV-1 integrase and human lens epithelium-derived growth factor (LEDGF/p75). Journal of Biomolecular Structure and Dynamics 36(12): 3199-3217, 2017

Discovery of Selective Small-Molecule Inhibitors for the β-Catenin/T-Cell Factor Protein-Protein Interaction through the Optimization of the Acyl Hydrazone Moiety. Journal of Medicinal Chemistry 58(11): 4678-4692, 2015