8-クロロジベンゾ[b,f][1,4]オキサゼピン-10(11H)-カルボン酸2-アセチルヒドラジド

The prostaglandin E2 (PGE2) receptor EP1 is involved in triggering PGE2-mediated pain, neuronal survival and growth as well as the suppression of tumor metastasis. SC-19220 is a dibenzoxazepine that acts as a selective antagonist of PGE2 at the EP1 receptor. At doses between 0.3-300 μM, SC-19220 acts as a competitive antagonist of PGE2-induced smooth muscle contractions of guinea pig ileum and stomach. SC-19220 also acts as a PGE2 antagonist in the EP1 receptor-mediated contraction of guinea pig trachea. SC-19220 displaces radiolabeled PGE2 from the cloned human EP1 receptor with an IC50 of 6.7 μM and exhibits no binding at the human EP2 receptor. It binds with apparent low affinity to the cloned mouse EP1 receptor expressed in CHO cells. In a model of bone resorption, 3-150 μM SC-19220 inhibited both 1,25 dihydroxy vitamin D3- and PGE2-stimulated osteoclastogenesis in mouse osteoclast precursors. Antagonism of EP1 with 1 μM SC-19220 has been shown to promote metastasis in a mouse model of metastatic breast cancer. In a rodent model of Parkinson’s disease, 1.5 μM SC-19220 prevented PGE2-mediated loss of dopaminergic neurons from rat substantia nigra.