Compound 54149 is novel positive allosteric modulator (PAM) of calcium sensing receptor (CaSR) with EC50 of 41 nM.
Compound 54149 stabilizes a distinct active-state CaSR dimer conformation.
Compound 54149 suppresses PTH secretion better than the approved PAM drugs, inhibits PTH secretion dose-dependently (IC50=583 nM) in extracted parathyroid glands from wild-type (WT) C57/BL6 (B6) mice.
Compound 54149 reduces serum PTH at lower doses with less hypocalcemia than cinacalcet and evocalcet.
