TG4-155 is a brain penetrant EP2 antagonist (KB = 2.4 nM) that is over 1000-fold less effective at EP4 (KB = 11.4 μM) and a panel of other receptors and channels

EP2 receptor:9.9 nM (Ki)

TG4-155 is a brain penetrant EP2 antagonist (KB = 2.4 nM) that is over 1000-fold less effective at EP4 (KB = 11.4 μM) and a panel of other receptors and channels[1].

TG4-155 significantly reduces neurodegeneration in a mouse model of status epilepticus, induced by pilocarpine. It inhibits proliferation, invasion, and inflammatory cytokine expression in cancer cells treated with butaprost[2].

Cytotoxicity of TG4-155 was examined with the CellTiter-Glo Luminescent Cell Viability Assay by measuring cellular ATP level, which correlates with cell viability.?Briefly, C6G cells were plated in 384-well plates at 2,000 cells/well in 25 μl DMEM plus test compound and incubated for 2 days.?CellTiter-Glo reagent (25 μl) was then added to each well.?The contents were mixed for 2 minutes on an orbital shaker to induce cell lysis and incubated at room temperature for 10 minutes.?Relative viability is proportional to luminescence intensity as measured by a microplate reader with an integration time of 1 second[2].

C57BL/6 mice (8 12 wk old) were injected with pilocarpine (280 mg/kg, i.p.) to induce status epilepticus (SE). SE was allowed for 1 h and terminated by pentobarbital (30 mg/kg, i.p.). Mice were then randomized by assignment to a random number stream and received two doses of vehicle or TG4-155 (5 mg/kg, i.p.) at 1 and 12 h after SE termination. Mice were euthanized under deep isoflurane anesthesia 24 h after SE and brains were collected for histology[1].