Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist

Herman D Lim; Rogier A Smits; Remko A Bakker; Cindy M E van Dam; Iwan J P de Esch; Rob Leurs

doi:10.1021/jm060880d

Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist

J Med Chem. 2006 Nov 16;49(23):6650-1. doi: 10.1021/jm060880d.

Authors

Herman D Lim¹, Rogier A Smits, Remko A Bakker, Cindy M E van Dam, Iwan J P de Esch, Rob Leurs

Affiliation

¹ Leiden/Amsterdam Center for Drug Research, Department of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.

PMID: 17154494
DOI: 10.1021/jm060880d

Abstract

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.

MeSH terms

Cell Line, Tumor
Guanidines / chemical synthesis*
Guanidines / chemistry
Guanidines / pharmacology
Histamine Agonists / chemical synthesis*
Histamine Agonists / chemistry
Histamine Agonists / pharmacology
Humans
Radioligand Assay
Receptors, G-Protein-Coupled / agonists*
Receptors, Histamine
Receptors, Histamine H4
Structure-Activity Relationship
Thiourea / analogs & derivatives*
Thiourea / chemical synthesis
Thiourea / chemistry
Thiourea / pharmacology
beta-Galactosidase / metabolism

Substances

Guanidines
HRH4 protein, human
Histamine Agonists
Receptors, G-Protein-Coupled
Receptors, Histamine
Receptors, Histamine H4
S-(2-guanidylethyl)isothiourea
beta-Galactosidase
Thiourea