880546-17-8

K-14585 is a proteinase-activated receptor 2 antagonist. Pretreatment with K-14585 inhibited PAR(2)-mediated p65 NFkappaB phosphorylation and NFkappaB-DNA binding. K-14585 inhibited SLIGKV-stimulated IL-8 production, but given alone increased IL-8. K-14585 antagonized PAR(2) competitively, resulting in inhibition of PAR(2)-mediated signalling and physiological responses both in vitro and in vivo. K-14585 could be useful in evaluating PAR(2)-mediated biological events and might lead to a new generation of therapeutically useful antagonists.

K-14585 is a peptide competitive PAR2 antagonist. K-14585 inhibits PAR2-dependent IL-8 production, NF-κB phosphorylation, and p38 signaling. K-14585 reduces SLIGKV (PAR2 agonist peptide)-induced Ca2+ mobilisation in primary human keratinocytes[1][2][3].

PAR2

[1] Goh FG, et al. Dual effect of the novel peptide antagonist K-14585 on proteinase-activated receptor-2-mediated signalling. Br J Pharmacol. 2009 Dec;158(7):1695-704. DOI:10.1111/j.1476-5381.2009.00415.x
[2] Kanke T, et al. Novel antagonists for proteinase-activated receptor 2: inhibition of cellular and vascular responses in vitro and in vivo. Br J Pharmacol. 2009 Sep;158(1):361-71. DOI:10.1111/j.1476-5381.2009.00342.x
[3] Sevigny LM, et al. Interdicting protease-activated receptor-2-driven inflammation with cell-penetrating pepducins. Proc Natl Acad Sci U S A. 2011 May 17;108(20):8491-6. DOI:10.1073/pnas.1017091108