Prostaglandin E2 (PGE2) evokes distinct responses through four different ‘E prostanoid’ (EP) receptors. EP2 is a G protein-coupled receptor that has diverse roles, including those in cancer, inflammation, and neuroprotection. 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. It blocks the induced expression of inflammatory markers in microglial cells treated with the selective EP2 agonist butaprost alone or with LPS and IFNγ. 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.
TG4-155 is a pharmacological agent which reduces neurodegeneration in a mouse model status of epilepticus induced by pilocarpine. Inhibits proliferation, inflammatory cytokine expression in cancer cells.
using a set of cell-based tr-fret assays of camp formation, a previous study screened a small molecule library and identified tg4-155 and tg4-166 as the most potent ones. tg4-155 and tg4-166 also showed robust inhibition of pge2 -induced camp accumulation in human ep2-overexpressing c6 glioma cells, without affecting prostaglandin ep4 or β2-adrenergic receptors. both tg4-155 and tg4-166 could cause a robust rightward shift in the pge2 dose–response curve without affecting the maximal response to pge2. tg4-155 at 1 μm caused 1,120-fold shift and tg4-166 at 1 μm caused a 651-fold shift in the pge2 ec50 [1].
tg4-155 could significantly reduced neuronal injury in hippocampus when administered in mice beginning 1 h after termination of pilocarpine-induced status epilepticus. the salutary actions of tg4-155 raised the possibility that selective block of ep2 signaling through small molecules can be an innovative therapeutic strategy for inflammation-related brain injury [1].
2.4 nm for kb ep2; 11.4 nm for kb ep4
[1] JIANXIONG JIANG R D. Role of prostaglandin receptor EP2 in the regulations of cancer cell proliferation, invasion, and inflammation.[J]. Journal of Pharmacology and Experimental Therapeutics, 2013, 344 2: 360-367. DOI:
10.1124/jpet.112.200444[2] YI QUAN Ray D Jianxiong Jiang. EP2 receptor signaling pathways regulate classical activation of microglia.[J]. The Journal of Biological Chemistry, 2013, 288 13: 9293-9302. DOI:
10.1074/jbc.m113.455816
