Uses
JNJ10191584 (VUF6002) is an orally active and selective histamine H4 receptor antagonist with a Ki value of 26 nM. JNJ10191584 shows 540-fold selectivity to H4 receptor over H3 receptor with a Ki value of 14.1 μM. JNJ10191584 inhibits chemotaxis of eosinophils and mast cells with IC50 values of 530 nM and 138 nM, respectively[1][2].
Definition
ChEBI: (6-chloro-1H-benzimidazol-2-yl)-(4-methyl-1-piperazinyl)methanone is a member of benzimidazoles.
in vivo
JNJ10191584 (10 μg/μL; intra locus coeruleus (LC) administration; once) abolishs VUF-induced anti-allodynic effect in spared nerve injury (SNI) mice[1].
JNJ10191584 (10 μg/μL; intra LC administration; once) prevents the anti-allodynic effect of VUF 8430 in SNI mice[1].
JNJ10191584 (6 μg/mouse; intrathecal administration; pretreat once) prevents VUF 8430-induced anti-allodynic effect in SNI mice[1].
IC 50
Human H
4 Receptor: 26 nM (Ki); human H
3 receptor: 14.1 μM (Ki)
References
[1] Venable JD, et al. Preparation and biological evaluation of indole, benzimidazole, and thienopyrrole piperazine carboxamides: potent human histamine h(4) antagonists. J Med Chem. 2005 Dec 29;48(26):8289-98. DOI:
10.1021/jm0502081[2] Sanna MD, et al. Histamine H4 receptor stimulation in the locus coeruleus attenuates neuropathic pain by promoting the coeruleospinal noradrenergic inhibitory pathway. Eur J Pharmacol. 2020 Feb 5;868:172859. DOI:
10.1016/j.ejphar.2019.172859