title: Allosteric inhibitors of plasma membrane Ca pumps: Invention and applications of caloxins.
abstract: Plasma membrane Ca(2+) pumps (PMCA) play a major role in Ca(2+) homeostasis and signaling by extruding cellular Ca(2+) with high affinity. PMCA isoforms are encoded by four genes which are expressed differentially in various cell types in normal and disease states. Therefore, PMCA isoform selective inhibitors would aid in delineating their role in physiology and pathophysiology. We are testing the hypothesis that extracellular domains of PMCA can be used as allosteric targets to obtain a novel class of PMCA-specific inhibitors termed caloxins. This review presents the concepts behind the invention of caloxins and our progress in this area. A section is also devoted to the applications of caloxins in literature. We anticipate that isoform-selective caloxins will aid in understanding PMCA physiology in health and disease. With strategies to develop therapeutics from bioactive peptides, caloxins may become clinically useful in cardiovascular diseases, neurological disorders, retinopathy, cancer and contraception.
authors.affiliation: Jyoti Pande, Ashok K Grover, Department of Medicine, HSC 4N41, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Pande
authors.forename: Magdalena M
authors.initials: MM
authors.lastname: Szewczyk
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Grover