ABALOPARATIDE TFA

Parathyroid hormone receptor 1 (PTHR1)

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 EC ₅₀ value for cAMP formation compared to teriparatide ( EC ₅₀ s of 0.3 nM and 0.7 nM, respectively).
A dose-dependent stimulation of β-arrestin/PTHR1 interaction is demonstrated by abaloparatide. Consistently, the calculates the EC ₅₀ value for abaloparatide is 1.6-fold lower than that of teriparatide ( EC ₅₀ s of 0.9 nM and 1.5 nM, respectively).
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 EC ₅₀ value of 0.8 nM for Abaloparatide.

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.