Assay strategies for identification of therapeutic leads that target protein trafficking.

Conn PM, Spicer TP, Scampavia L, Janovick JA
Trends Pharmacol Sci. 2015 36 (8): 498-505

PMID: 26067100 · PMCID: PMC4532603 · DOI:10.1016/j.tips.2015.05.004

Receptors, enzymes, and ion channels are traditional targets of therapeutic development. A common strategy is to target these proteins with agents that either activate or suppress their activity with ligands or substrates that occupy orthosteric sites or have allosteric interactions. An alternative approach involves regulation of protein trafficking. In principle, this approach enables 'rescue' of misfolded and misrouted mutant proteins to restore function, 'shipwrecking' of undesirable proteins by targeting them for destruction, and regulation of levels of partially expressed wild type (WT) proteins at their functional sites of action. Here, we present drug discovery strategies that identify 'pharmacoperones', which are small molecules that serve as molecular templates and cause otherwise misfolded mutant proteins to fold and route correctly.

Copyright © 2015 Elsevier Ltd. All rights reserved.

MeSH Terms (8)

Animals Drug Discovery High-Throughput Screening Assays Humans Protein Folding Protein Transport Receptors, G-Protein-Coupled Small Molecule Libraries

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