ArticleChemistry & biology2010
hCB2 ligand-interaction landscape: cysteine residues critical to biarylpyrazole antagonist binding motif and receptor modulation.
Article in Chemistry & biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Covalent cannabinoid receptor ligands - structural insight and selectivity challenges.RSC medicinal chemistry · 2022Review
- Design and Characterization of an Intracellular Covalent Ligand for CC Chemokine Receptor 2.Journal of medicinal chemistry · 2021Article
- Functionalized Cannabinoid Subtype 2 Receptor Ligands: Fluorescent, PET, Photochromic and Covalent Molecular Probes.ChemMedChem · 2020Review
- Covalent Inhibition of the Histamine HMolecules (Basel, Switzerland) · 2019Article
- Article
- Binding Site Characterization of AM1336, a Novel Covalent Inverse Agonist at Human Cannabinoid 2 Receptor, Using Mass Spectrometric Analysis.Journal of proteome research · 2017Article
- Article
- Review
- Molecular-interaction and signaling profiles of AM3677, a novel covalent agonist selective for the cannabinoid 1 receptor.ACS chemical neuroscience · 2015Article
- 3'-functionalized adamantyl cannabinoid receptor probes.Journal of medicinal chemistry · 2015Article
- Species differences in cannabinoid receptor 2 and receptor responses to cocaine self-administration in mice and rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Article
- High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875.Nature · 2014Article
- 2012 Division of medicinal chemistry award address. Trekking the cannabinoid road: a personal perspective.Journal of medicinal chemistry · 2014Article
- Design and pharmacological characterization of VUF14480, a covalent partial agonist that interacts with cysteine 98(3.36) of the human histamine H₄ receptor.British journal of pharmacology · 2013Article
- Methods for recombinant expression and functional characterization of human cannabinoid receptor CB2.Computational and structural biotechnology journal · 2013Review
- Mass spectrometry-based proteomics of human cannabinoid receptor 2: covalent cysteine 6.47(257)-ligand interaction affording megagonist receptor activation.Journal of proteome research · 2011Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
The human cannabinoid 2 GPCR (hCB2) is a prime therapeutic target. To define potential cysteine-related binding motifs critical to hCB2-ligand interaction, a library of hCB2 cysteine-substitution mutants and a novel, high-affinity biarylpyrazole hCB2 antagonist/inverse agonist (AM1336) functionalized to serve as a covalent affinity probe to target cysteine residues within (or in the microenvironment of) its hCB2 binding pocket were generated. The data provide direct experimental demonstration that both hCB2 TMH7 cysteines [i.e., C7.38(284) and C7.42(288)] are critical to optimal hCB2-AM1336 binding interaction and AM1336 pharmacological activity in a cell-based functional assay (cAMP formation). Elongating the AM1336 aliphatic side chain generated another novel hCB2 inverse agonist that binds covalently and selectively to C7.42(288) only. Identification of specific cysteine residues critical to hCB2 ligand interaction and function informs the structure-based design of hCB2-targeted medicines.
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Registered trials
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