GW 627368

GW627368(GW627368X) is a novel, potent and selective competitive antagonist of prostanoid EP4 receptor(Ki= 100 nM) with additional human TP receptor affinity(Ki= 150 nM).IC50 value: Target: EP4 antagonistin vitro: At recombinant human prostanoid EP4 receptors expressed in HEK293 cells, GW627368X produced parallel rightward shifts of PGE2 concentration-effect (E/[A]) curves resulting in an affinity (pKb) estimate of 7.9 +/- 0.4. GW627368X appears to bind to human prostanoid TP receptors but not the TP receptors of other species. In human washed platelets, GW627368X (10 microM) produced 100% inhibition of U-46619 (EC100)-induced aggregation (approximate pA2 approximately 7.0) [1]. in vivo: Oral administration of GW627368X showed significant tumor regression characterized by tumor reduction and induction of apoptosis. Reduction in prostaglandin E2 synthesis also led to reduced level of VEGF in plasma [2].

Signaling Pathways >> GPCR/G Protein >> Prostaglandin Receptor

Research Areas >> Inflammation/Immunology

[1]. Wilson RJ, et al. GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid EP4 receptor antagonist. Br J Pharmacol. 2006 Jun;148(3):326-39.

[2]. Parida S, et al. Molecular inhibition of prostaglandin E2 with GW627368X: Therapeutic potential and preclinical safety assessment in mouse sarcoma model. Cancer Biol Ther. 2015 Jun 3;16(6):922-32.

[3]. Mason KL, et al. Intrauterine group A streptococcal infections are exacerbated by prostaglandin E2. J Immunol. 2013 Sep 1;191(5):2457-65.

Dinoprostone | Prostaglandin E1 | E7046 | ONO-AE3-208 | PF 04418948 | Fevipiprant | grapiprant | TG6-10-1 | Taprenepag | MRE-269 | Ramatroban | AH 6809 | Laropiprant | AZD1981 | Evatanepag