TG4-155 is a potent, brain-permeant and selective EP2 receptor antagonist with a Ki of 9.9 nM[2]. TG4-155 shows low nanomolar antagonist activity against only EP2 and DP1. TG4-155 has an EP2 Schild KB of 2.4 nM and displays 550-4750-fold selectivity for EP2 over EP1, EP3, EP4 and IP, but only 14-fold selectivity against the DP1 receptor[2].In Vitro: TG4-155 inhibits the serotonin 5-HT2B receptor with IC50=2.6 μM and hERG (human Ether-à-go-go-Related Gene) with IC50=12 μM.
PGE2 (0.1-10 μM) stimulation significantly enhances human prostate cancer cell line PC3 cell growth in a concentration-dependent manner with a maximal response being obtained at approximately 1 μM. This PGE2-induced cancer cell proliferation is significantly suppressed by TG4-155 (0.01-1μM ; 48 hours) in a concentration-dependent manner.In Vivo: Administration of TG4-155 (5 mg/kg, i.p.; at 1 and 12 h) significantly reduces status epilepticus (SE)-induced neurodegeneration scores in C57BL/6 mice.
TG4-155 (3 mg/kg; i.p.) displays a bioavailability of 61% (i.p. route compared with i.v.), a plasma half-life (t1/2) of 0.6 h, and a brain/plasma ratio of 0.3 in C57BL/6 mice.