@article {M.C. Meireles:2011:1568-0266:248,
title = "Discovery of Modulators of Protein-Protein Interactions: Current Approaches and Limitations",
journal = "Current Topics in Medicinal Chemistry",
parent_itemid = "infobike://ben/ctmc",
publishercode ="ben",
year = "2011",
volume = "11",
number = "3",
publication date ="2011-02-01T00:00:00",
pages = "248-257",
itemtype = "ARTICLE",
issn = "1568-0266",
url = "https://www.ingentaconnect.com/content/ben/ctmc/2011/00000011/00000003/art00002",
doi = "doi:10.2174/156802611794072632",
keyword = "Bcl-2 family, low-affinity binders, DNA replication, signal transduction, WW, allosteric binding sites, isothermal titration calorimetry, drug discovery, smMLCK, turns, Myc-Max dimer, sheets, HCS assays, Nuclear magnetic resonance (NMR)spectroscopy, SMAC, human serum albumin, ABT-737, small-molecule modulators, PDZ, ligands, HDM2, hotspots, anti-apoptotic members, cIAP-2, turn mimetic scaffolds, biochemical assay, small molecules, c-Myc-Max heterodimer, Trp800, mass spectrometry, high-throughput screening, undruggable, Ligand-based drug discovery, Janus kinases 2, Bcl-XL, SH3, receptor-based pharmacophore, calmodulin, Alpha-helices, lymphomas, surface plasmon resonance (SPR), tumorigenesis, Val807, erythropoietin, Multiple Protein Structure, cIAP-1, peptide based drug discovery, fragment-based drug discovery, BH3-helix, X-ray crystallography (XRC), Thr803, HematideTM, IC50 9 nM, PTB, Normal Mode Analyses, hematopoietic growth hormone, lung cancer, tri-substituted imidazole backbone, p53, ligandbased pharmacophore, Bcl-2, protein secondary structure mimetics, tumor suppressor protein, computer-aided drug discovery, cancer, tethering, SH2, p53-MDM2/HDM2, Protein-protein interactions, terephthalamide scaffold",
author = "M.C. Meireles, Lidio and Mustata, Gabriela",
abstract = "Protein-protein interactions are involved in most of the essential processes that occur in living organisms from cell motility to DNA replication, which makes them interesting targets for drug discovery. However, due to the lack of deep pockets, and the large contact surfaces involved in these interactions, they are considered challenging targets and have been often times dismissed as undruggable. Nonetheless, significant efforts in pharmaceutical and academic laboratories have been devoted to finding ways to exploit protein-protein interactions as drug targets. This article provides an overview of the principles underlying the main general strategies for discovering small-molecule modulators of protein-protein interactions, namely: high-throughput screening, fragment-based drug discovery, peptide-based drug discovery, protein secondary structure mimetics, and computer-aided drug discovery. In addition, examples of successful discovery of modulators of protein-protein interactions are discussed for each of those strategies. ",
}