Org 214444-0 is a highly potent, selective, allosteric agonist of follicle stimulating hormone receptor (FSHR) with EC50 of 2.0/1.2 nM (human/rat FSHR) in cell-based assays.
Org 214444-0 stimulates cAMP synthesis in cell line expressing human FSHR with EC50 of 5 nM in cAMP assays, Emax of 102%.
Org 214444-0 displays >200-fold selective over the human and rat LHR, and does not activate the human TSHR.
Org 214444-0 has also negligible antagonistic activity at the human and rat LHR and human TSHR at 1 uM.
Org 214444-0 is an allosteric agonist interacting with the transmembrane region of the FSHR.
When co-incubated with FSH, Org 214444-0 augments FSH's potency in binding (6.5-fold) and adenylyl cyclase/cAMP activation (3.5-fold) in a concentration-dependent manner.
Org 214444-0 induces FSHR internalization and is only marginally effective in stimulating phospholipase C.
Org 214444-0 stimulates cAMP and estradiol production in human granulosa cells in culture and supports the follicular phase in mature female rats.