2-[(Aminoiminomethyl)amino]ethyl carbamimidothioic acid ester (S-(2-guanidylethyl)-isothiourea; VUF 8430 dihydrobromide) 

VUF 8430 dihydrobromide is a potent histamine H4 receptor full agonist (pEC50 = 7.3), high affinity (pKi = 7.5)

OTAVAchemicals Catalogue Number: 7070707134

CAS Registry Number: 100130-32-3

CAS Registry Number: 98021-17-1 (free base)

Purity: 97%+

Ref. 1:  Sterk et al. Studies on histaminergic compounds. IV. Non-isosterism between the imidazole, guanidino and isothiourea moieties at the H₂-receptor. Archiv der Pharmazie (Weinheim, Germany) (1986), 319, 1057-1064

Abstract: S,S'-Alkylenediisothioureas were found to show only weak agonistic or antagonistic H₂-activity, depending on the length of the alkylene chain. Introduction of a substituent in the amidino parts of both isothiourea groups resulted in a complete loss of the agonistic activity; only inactive compounds or weakly active H₂-antagonists were obtained. Replacing one of the isothiourea groups of the alkylenediisothioureas with n = 2, 3 or 4 by a guanidino group has hardly any or no effect at all on the histamine H₂-activity on the guinea-pig right atrium. However, extending the alkylene chain of these guanidylalkylisothioureas to n = 5 and 6 results in a strong increase in the H₂-agonistic activity

Ref. 2: Lim et al. Pharmacological characterization of the new histamine H₄ receptor agonist VUF
8430. British Journal of Pharmacology (2009), 157, 34-43

Background and purpose: We compare the pharmacological profiles of a new histamine H₄ receptor agonist 2-(2-guanidinoethyl)isothiourea (VUF 8430) with that of a previously described H₄ receptor agonist, 4-methylhistamine. 
Experimental approach: Radioligand binding and functional assays were performed using histamine H₄ receptors expressed in mammalian cell lines. Compounds were also evaluated ex vivo in monocyte-derived dendritic cells endogenously expressing H₄ receptors and in vivo in anaesthetized rats for gastric acid secretion activity. 
Key results: Both VUF 8430 and 4-methylhistamine were full agonists at human H4 receptors with lower affinity at rat and mouse H4 receptors. Both compounds induced chemotaxis of monocyte-derived dendritic cells. VUF 8430 also showed reasonable affinity and was a full agonist at the H3 receptor. Agmatine is a metabolite of arginine, structurally related to VUF 8430, and was a H₄ receptor agonist with micromolar affinity. At histamine H₃ receptors, agmatine was a full agonist, whereas 4-methylhistamine was an agonist only at high concentrations. Both VUF 8430 and agmatine were inactive at H₁ and H₂ receptors, whereas 4-methylhistamine is as active as histamine at H₂ receptors. In vivo, VUF 8430 only caused a weak secretion of gastric acid mediated by H2 receptors, whereas 4-methylhistamine, dimaprit, histamine and amthamine, at equimolar doses, induced 2.5- to 6-fold higher output than VUF 8430. 
Conclusions and implications: Our results suggest complementary use of 4-methylhistamine and VUF 8430 as H₄ receptor agonists. Along with H₄ receptor antagonists, both agonists can serve as useful pharmacological tools in studies of histamine H₄ receptors.

Ref. 3: Lim et al. Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H₄ receptor agonist. Journal of Medicinal Chemistry (2006), 49, 6650-6651

Abstract: During an inhouse database screen, the authors 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 pharmacol. tool that enables further unraveling of the physiol. roles of the H₄ receptor.

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