TG4-155

TG4-155 is a potent, brain-permeant and selective EP2 receptor antagonist with a K_i of 9.9 nM^[1][2]. TG4-155 shows low nanomolar antagonist activity against only EP2 and DP1^[1]. TG4-155 has an EP2 Schild K_B 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^[1].
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^[1]. 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^[3].
TG4-155 (3 mg/kg; i.p.) displays a bioavailability of 61% (i.p. route compared with i.v.), a plasma half-life (t_1/2) of 0.6 h, and a brain/plasma ratio of 0.3 in C57BL/6 mice^[3].