7,7-DIFLUOROPROSTACYCLIN DERIVATIVE, AFP-07, A HIGHLY SELECTIVE AND POTENT AGONIST FOR THE PROSTACYCLIN RECEPTOR

Recently, we cloned cDNAs for the prostacyclin receptor (IP) and the f our mouse PGE receptor subtypes, EP1, EP2, EP3 and EP4, and establishe d Chinese hamster ovary cells that stably express each receptor. We ex amined the agonist potency and selectivity of AFP-07, a 7,7-difluoropr ostacyclin derivative, compared with widely used stable prostacyclin a nalogue, iloprost, using the cells expressing each cloned receptor. AF P-07 strongly displaced the [H-3] iloprost binding to the IP receptor- expressing cell membranes, the half maximal concentration for the disp lacement being 3 nM, which was one order lower than that of iloprost. AFP-07 concentration-dependently stimulated cAMP formation in the IP-e xpressing cells, the half-maximal concentration for the stimulation be ing 10 pM, which was one order lower than that of iloprost. On the oth er hand, AFP-07 showed lower affinity for EP1, EP2, EP3 and EP4 than P GE(2), but iloprost had the same affinity as PGE(2) for the EP1. These results demonstrate that AFP-07 is a potent and highly selective agon ist for the IP receptor. (C) 1997 by Elsevier Science Inc.