Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist.
During an in-house database screen, we identified S-(2-guanidylethyl)-isothiourea as a high affinity agonist for the histamine H4 receptor, with a 33-fold selectivity over the histamine H3 receptor and negligible affinity for the other histamine receptor subtypes. This nonimidazole ligand is introduced as a useful and complementary pharmacological tool that enables further unraveling of the physiological roles of the H4 receptor.
Lim
Herman D
HD
Leiden/Amsterdam Center for Drug Research, Department of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Smits
Rogier A
RA
Bakker
Remko A
RA
van Dam
Cindy M E
CM
de Esch
Iwan J P
IJ
Leurs
Rob
R
D045744:Cell Line, Tumor; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017442:Histamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism
D006146:Guanidines; C418607:HRH4 protein, human; D017442:Histamine Agonists; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C516215:S-(2-guanidylethyl)isothiourea; D001616:beta-Galactosidase; D013890:Thiourea