{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nijmeijer S"],"funding":["Dutch Research Council (NWO)"],"pagination":["89-100"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3764852"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["170(1)"],"pubmed_abstract":["<h4>Background and purpose</h4>The recently proposed binding mode of 2-aminopyrimidines to the human (h) histamine H₄ receptor suggests that the 2-amino group of these ligands interacts with glutamic acid residue E182(5.46) in the transmembrane (TM) helix 5 of this receptor. Interestingly, substituents at the 2-position of this pyrimidine are also in close proximity to the cysteine residue C98(3.36) in TM3. We hypothesized that an ethenyl group at this position will form a covalent bond with C98(3.36) by functioning as a Michael acceptor. A covalent pyrimidine analogue will not only prove this proposed binding mode, but will also provide a valuable tool for H4 receptor research.<h4>Experimental approach</h4>We designed and synthesized VUF14480, and pharmacologically characterized this comp"],"journal":["British journal of pharmacology"],"pubmed_title":["Design and pharmacological characterization of VUF14480, a covalent partial agonist that interacts with cysteine 98(3.36) of the human histamine H₄ receptor."],"pmcid":["PMC3764852"],"funding_grant_id":["700.59.408"],"pubmed_authors":["Haaksma EE","Schultes S","de Graaf C","Nijmeijer S","Wijtmans M","Vischer HF","Leurs R","van de Stolpe AC","Lusink V","Engelhardt H","de Esch IJ","Stachurski K"],"additional_accession":[]},"is_claimable":false,"name":"Design and pharmacological characterization of VUF14480, a covalent partial agonist that interacts with cysteine 98(3.36) of the human histamine H₄ receptor.","description":"<h4>Background and purpose</h4>The recently proposed binding mode of 2-aminopyrimidines to the human (h) histamine H₄ receptor suggests that the 2-amino group of these ligands interacts with glutamic acid residue E182(5.46) in the transmembrane (TM) helix 5 of this receptor. Interestingly, substituents at the 2-position of this pyrimidine are also in close proximity to the cysteine residue C98(3.36) in TM3. We hypothesized that an ethenyl group at this position will form a covalent bond with C98(3.36) by functioning as a Michael acceptor. A covalent pyrimidine analogue will not only prove this proposed binding mode, but will also provide a valuable tool for H4 receptor research.<h4>Experimental approach</h4>We designed and synthesized VUF14480, and pharmacologically characterized this comp","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Sep","modification":"2026-05-06T21:35:13.007Z","creation":"2026-04-07T22:21:39.073Z"},"accession":"S-EPMC3764852","cross_references":{"pubmed":["23347159"],"doi":["10.1111/bph.12113"]}}