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- W2154249927 endingPage "184" @default.
- W2154249927 startingPage "165" @default.
- W2154249927 abstract "The presence of druggable, topographically distinct allosteric sites on a wide range of receptor families has offered new paradigms for small molecules to modulate receptor function. Moreover, ligands that target allosteric sites offer significant advantages over the corresponding orthosteric ligands in terms of selectivity, including subtype selectivity within receptor families, and can also impart improved physicochemical properties. However, allosteric ligands are not a panacea. Many chemical issues (e.g., flat structure-activity relationships) and pharmacological issues (e.g., ligand-biased signaling) that are allosteric centric have emerged. Notably, the fact that allosteric sites are less evolutionarily conserved leads to improved selectivity; however, this can also lead to species differences that can hinder safety assessment. Many allosteric ligands possess molecular switches, wherein a small structural change (chemical or metabolic) can modulate the mode of pharmacology or receptor subtype selectivity. As the field has matured, as described here, key principles and strategies have emerged for the design of ligands/drugs for allosteric sites." @default.
- W2154249927 created "2016-06-24" @default.
- W2154249927 creator A5037017761 @default.
- W2154249927 creator A5047118594 @default.
- W2154249927 creator A5060483072 @default.
- W2154249927 creator A5077505426 @default.
- W2154249927 date "2014-01-06" @default.
- W2154249927 modified "2023-10-18" @default.
- W2154249927 title "Drugs for Allosteric Sites on Receptors" @default.
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- W2154249927 doi "https://doi.org/10.1146/annurev-pharmtox-010611-134525" @default.
- W2154249927 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4063350" @default.
- W2154249927 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24111540" @default.
- W2154249927 hasPublicationYear "2014" @default.