14-Anhydrodigitoxigenin is a cardenolide and a derivative of digitoxin.1 It reduces the activity of guinea pig heart Na+/K+-ATPase by 15% when used at a concentration of 10 μM.2
Tenellin is a fungal metabolite that inhibits Mg2+-, Ca2+-, and Na+ K+-ATPase activities in erythrocytes. Tenellin is cytotoxic to Sf9 and Sf21 insect cells.
Citreoviridin, a toxin from Penicillium citreoviride NRRL 2579, inhibits brain synaptosomal Na+ K+-ATPase whereas, in microsomes, both Na+ K+-ATPase and Mg2+-ATPase activities are significantly stimulated in a dose-dependent manner.
Bassianin, a fungal metabolite identified in Beauveria, demonstrates inhibition of Mg2+-, Ca2+-, and Na+/K+-ATPase activities in equine erythrocyte ghosts, with inhibition rates of 81%, 58%, and 23%, respectively, at a concentration of 200 µg/ml. Additionally, bassianin exhibits cytotoxic properties against Sf9 and Sf21 insect cells, with 50% cytotoxic concentration (CC50) values of 4.91 µM and 12.12 µM, respectively.
Caloxin 2A1 TFA is a peptide inhibitor specifically targeting the extracellular plasma membrane Ca2+-ATPase (PMCA), without influencing the basal activities of Mg2+-ATPase or Na+-K+-ATPase[1].
Carsatrin succinate is the salt form of Carsatin, a purinylpiperazine derivative used as a cardiotonic and antiarrhythmic. Carsatrin acts as positive inotropic agent that increases twitch tension and prolongs the action potential (AP) duration of ventricular muscle without affecting the Na+, K+-ATPase, adenylyl cyclase, phosphodiesterase isozymes, or cardiac myofilaments. Carsatrin’s positive inotropic effect can be prevented by tetrodotoxin but not by the adrenergic antagonists timolol, yohimbine, or prazosin.
Boromycin is a boron-containing macrolide antibiotic that has been found in Streptomyces. Boromycin inhibits growth of B. subtilis (MIC = 0.05 μg ml) and induces efflux of potassium ions from B. subtilis without affecting Na+ K+-ATPase activity. It decreases the synthesis of protein, RNA, and DNA in B. subtilis when used at a concentration of 0.05 μg ml. It inhibits the growth of B. halodurans (MIC = 10 ng ml) and inhibits the futalosine pathway of menaquinone synthesis in B. halodurans. Boromycin (3.4 nM) reverses bleomycin-induced cell cycle arrest at the G2 phase in Jurkat cells. It inhibits replication of the HIV-1 strains LAV-1 and RF and the HIV-2 strain LAV-2 in MT-4 cells (IC50s = 0.008, 0.11, and 0.007 μM, respectively). It also inhibits replication of a clinical isolate of HIV-1, strain KK-1, in MT-4 cells and peripheral blood mononuclear cells (PBMCs; IC50s = 0.14 and <0.1 μM, respectively).
11-Dehydrocorticosterone is an endogenous mineralocorticoid. It increases Na+/K+-ATPase mRNA expression in vascular smooth muscle cells and inhibits aldosterone action in B. marinus toad bladder tissue in a concentration-dependent manner. 11-Dehydrocorticosterone decreases the sodium/creatine ratio and increases the potassium/creatine ratio in rat urine in a dose-dependent manner in a model of 11β-hydroxysteroid dehydrogenase inhibition induced by carbenoxolone. Chronic administration 11-dehydrocorticosterone increases plasma glucocorticoids levels, body weight gain, and adiposity, as well as induces insulin resistance in mice.
Caloxin 2A1 is an inhibitor peptide of the plasma membrane Ca 2+-ATPase (PMCA) responsible for extracellular signaling. Importantly, Caloxin 2A1 has no impact on the basal Mg 2+-ATPase or Na+-K+-ATPase activities.
Transdermal Peptide is a 11-amino acid peptide, binds to Na+/K+-ATPase beta-subunit (ATP1B1), and enhances the transdermal delivery of many macromolecules. Transdermal Peptide (TD1) binds to ATP1B1, and mainly interacts with the C-terminus of ATP1B1 in yeast and mammalian cells. The interaction affects the expression and localization of ATP1B1 and epidermal structure, but can be antagonized by the exogenous competitor ATP1B1 or be inhibited by ouabain. Inhibition of Transdermal Peptide binding to ATP1B1 causes decreased delivery of macromolecular drugs across the skin[1]. [1]. Wang C, et al. Role of the Na(+)/K(+)-ATPase beta-subunit in peptide-mediated transdermal drug delivery. Mol Pharm. 2015 Apr 6;12(4):1259-67.
Istaroxime, also known as PST-2744, is a positive inotropic agent that mediates its action through inhibition of sodium/potassium adenosine triphosphatase (Na+/K+ ATPase). Na+/K+ ATPase inhibition increases intracellular sodium levels, which reverses the driving force of the sodium/calcium exchanger, inhibiting calcium extrusion and possibly facilitating calcium entry. Additionally, Istaroxime increases intracellular calcium by improving the efficacy by which intracellular calcium triggers sarcoplasmic reticulum calcium release, and by accelerating the inactivation state of L-type calcium channels, which allow for calcium influx.
Nepaprazole Na is the salt form of Nepaprazole Free Base, also known as TY-11345, is a proton pump inhibitor potentially for treatment of gastric ulcer. TY-11345 potently inhibited H+/K(+)-ATPase activity in isolated rabbit gastric mucosal microsomes; and the inhibitory effect was enhanced under weak acid conditions, the IC50 (concentrations that inhibit the enzyme activity by 50%) being 5.8 microM and 9.9 microM at pH 6.0 and pH 7.4, respectively. TY-11345 should be useful for the clinical treatment of peptic ulcer diseases.
Carsatrin is purinylpiperazine derivative. as cardiotonic and antiarrhythmic. Carsatrin acts as positive inotropic agent that increases twitch tension and prolongs the action potential (AP) duration of ventricular muscle without affecting the Na+, K+-ATPase, adenylyl cyclase, phosphodiesterase isozymes, or cardiac myofilaments. Carsatrin’s positive inotropic effect can be prevented by tetrodotoxin but not by the adrenergic antagonists timolol, yohimbine, or prazosin
Germicidin A is a pyranone originally derived from S. viridochromogenes that acts as a reversible, autoregulative inhibitor of spore germination and hyphal elongation in the genus Streptomyces at concentrations as low as 200 pM. During germination, spores of Streptomyces excrete germicidin A along with other germicidin homologs, which inhibit germination of its own arthrospores. At higher concentrations, germicidin A can inhibit the porcine Na+/K+-activated ATPase (ID50 = 100 μM) and prevent the germination of the cress L. sativum.
Transdermal Peptide Disulfide TFA (TD 1 Disulfide(peptide) TFA), an 11-amino acid peptide, specifically binds to the Na+ K+-ATPase beta-subunit (ATP1B1), predominantly interacting with its C-terminus. This compound is capable of enhancing the transdermal delivery of various macromolecules[1].