Figure 1.

Schematic representation of the mechanism of action of NPS 2143. NPS 2143 binds to the TMD of plasma membrane-expressed CaSRs and decreases Ca²⁺_o-mediated signaling responses such as Ca²⁺_i mobilization. Prolonged exposure of CaSR-expressing cells to NPS 2143 may lead to the internalization of this calcilytic compound, which is considered to bind to newly formed CaSRs within the endoplasmic reticulum (ER), and destabilize their active conformation, thus leading to protein misfolding and proteasomal degradation (8), which would in turn diminish the pool of receptors available for trafficking to the plasma membrane. EC, extracellular.