PMCA3 Inhibitors

These inhibitors encompass a range of chemical classes, including SERCA pump inhibitors, calcium channel blockers, calmodulin antagonists, calcium chelators, and modulators of calcium release from intracellular stores. Thapsigargin, a SERCA pump inhibitor, disrupts calcium storage in the endoplasmic reticulum, leading to altered calcium signaling and potentially affecting PMCA3 activity indirectly. 2-APB and TMB-8 modulate various aspects of calcium signaling, including IP3 receptors and intracellular calcium levels, which can influence PMCA3's role in maintaining calcium homeostasis.

Calcium channel blockers such as Verapamil, Nifedipine, Nimodipine, and Amlodipine are well-known for their ability to modulate calcium influx across cell membranes. By altering calcium entry, these agents indirectly affect the calcium extrusion role of PMCA3. Calmidazolium chloride is a calmodulin antagonist; since PMCA3 activity is regulated by calmodulin, its inhibition can indirectly impact PMCA3 function. Similarly, BAPTA-AM, a calcium chelator, by modulating intracellular calcium levels, can influence the activity of PMCA3. Ryanodine and caffeine affect calcium release from intracellular stores, altering calcium dynamics within the cell and potentially impacting PMCA3's function in calcium extrusion. SKF-96365, as an inhibitor of store-operated calcium entry, also plays a role in modulating intracellular calcium levels, indirectly affecting PMCA3.