Abaloparatide acetate is a parathyroid hormone receptor 1 PTHR1 analogue and an effective and selective activator of the PTHR1 signaling pathway.

MC3T3-E1 osteoblast cells are treated with 0.01-100 nM of Abaloparatide for 40 min at 37 ℃ in the presence of 0.5 mM IBMX. The results reveals that exposure of cells to Abaloparatide caused a robust elevation of intracellular cAMP levels. Abaloparatide treatment results in a 2.3-fold decrease in EC50 value for cAMP formation compared to teriparatide (EC50s of 0.3 nM and 0.7 nM, respectively)[1]. A dose-dependent stimulation of β-arrestin/PTHR1 interaction is demonstrated by abaloparatide. Consistently, the calculates the EC50 value for abaloparatide is 1.6-fold lower than that of teriparatide (EC50s of 0.9 nM and 1.5 nM, respectively)[1]. Abaloparatide efficiently induces a dose-dependent stimulation of PTHR1 internalization with a dose as low as 0.1 nM and reaches maximum stimulation at 100 nM concentration. The EC50 value of 0.8 nM for Abaloparatide[1].

Abaloparatide (1-25 μg/kg; subcutaneous injection; daily; for 12 months; female Sprague-Dawley rats) treatment increases biochemical bone formation markers, histomorphometric indices of bone formation on trabecular, endocortical, and periosteal surfaces. Abaloparatide induces substantial increases in trabecular bone volume and density and improvements in trabecular microarchitecture. Abaloparatide stimulates periosteal expansion and endocortical bone apposition at the tibial diaphysis, leading to marked increases in cortical bone volume and density. Whole-body bone mineral density (BMD) is increasing 25% after 12 months of abaloparatide (25?μg/kg) in osteopenic ovariectomized (OVX) rats[2].