Druggable negative allosteric site of P2X3 receptors [PDF]
Proceedings of the National Academy of Sciences, 2018 SignificanceAllosteric regulation, produced by the binding of a ligand at an allosteric site topographically distinct from the orthosteric site, represents a direct and efficient means for modulation of biological macromolecule function. Because allosteric modulators have advantages over classic orthosteric ligands as therapeutic agents, understanding ...
Jin, Wang +13 more
openaire +2 more sources
Cyclic nucleotide-gated channels: structural basis of ligand efficacy and allosteric modulation [PDF]
, 1997 Most working proteins, including metabolic enzymes, transcription regulators, and membrane receptors, transporters, and ion channels, share the property of allosteric coupling. The term 'allosteric' means that these proteins mediate indirect interactions
Lester, Henry A. +2 more
core +1 more source
eLife, 2020 Pentameric ligand-gated ion channels (pLGICs) or Cys-loop receptors are involved in fast synaptic signaling in the nervous system. Allosteric modulators bind to sites that are remote from the neurotransmitter binding site, but modify coupling of ligand ...
Marijke Brams +12 more
doaj +1 more source
Molecules, 2021 The CB1 cannabinoid receptor (CB1R) contains one of the longest N termini among class A G protein-coupled receptors. Mutagenesis studies suggest that the allosteric binding site of cannabidiol (CBD) involves residues from the N terminal domain.
Jakub Jakowiecki +5 more
doaj +1 more source
The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs [PDF]
, 2013 G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential.
Hudson, Brian D. +2 more
core +1 more source
Allosteric Inhibition of Factor XIIIa. Non-Saccharide Glycosaminoglycan Mimetics, but Not Glycosaminoglycans, Exhibit Promising Inhibition Profile [PDF]
, 2016 Factor XIIIa (FXIIIa) is a transglutaminase that catalyzes the last step in the coagulation process. Orthostery is the only approach that has been exploited to design FXIIIa inhibitors.
Afosa, Daniel K. +4 more
core +8 more sources
Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I [PDF]
, 2012 Background: Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity.
Badura, Susanne +8 more
core +1 more source
Toxins, 2021 α-conotoxins are 13–19 amino acid toxin peptides that bind various nicotinic acetylcholine receptor (nAChR) subtypes. α-conotoxin Mr1.7c (MrIC) is a 17 amino acid peptide that targets α7 nAChR.
Alican Gulsevin +6 more
doaj +1 more source
Mapping the druggable allosteric space of G-protein coupled receptors: a fragment-based molecular dynamics approach. [PDF]
, 2010 To address the problem of specificity in G-protein coupled receptor (GPCR) drug discovery, there has been tremendous recent interest in allosteric drugs that bind at sites topographically distinct from the orthosteric site. Unfortunately, structure-based
Ivetac, Anthony, McCammon, J Andrew
core +2 more sources
Bitopic binding mode of an M1 muscarinic acetylcholine receptor agonist associated with adverse clinical trial outcomes [PDF]
, 2018 The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating ...
Bradley, Sophie J. +14 more
core +1 more source