Trends in Pharmacological Sciences
ForumDigoxin as an emerging therapy in noncardiac diseases
Section snippets
Overview of digoxin and drug repurposing
Digoxin is a CG (see Glossary) isolated from the purple foxglove Digitalis purpurea. Like other CGs, the structure of digoxin is conserved. CGs consist of a steroid ring bound to a lactone ring at position 17, with or without a sugar moiety at position 3. The steroid ring is present in all CGs and consists of 17 carbons arranged in four rings. The diversity of CGs arises from the number of carbons in the lactone ring, which determines their activity, and their associated sugar moieties, which
Concluding remarks and future directions
Repurposing of the CG digoxin for noncardiac indications is a very attractive strategy for several reasons, including cost and time savings. Digoxin has several decades of use in the cardiac arena; hence, knowledge accrued from its clinical use can be applied toward its repurposing for noncardiac diseases. Central to the well-known biologic activity of digoxin is its inhibitory effect on the Na,K-ATPase pump. Aside from its pump function, the Na,K-ATPase also functions as a signal transducer, a
Acknowledgments
Research in W.Z.M.’s laboratory is supported by National Institutes of Health U01 grant 5U01AA026962-02.
Declaration of interests
No interests are declared.
Glossary
- Cardiac glycoside (CG)
- a class of compounds that inhibit the Na,K-ATPase enzyme, increasing the output force of the heart and decreasing its rate of contractions. These properties are beneficial for treatment of congestive heart failure and cardiac arrhythmias.
- Cytokine storm
- a potentially harmful exaggerated immune response during which the body releases a large number of cytokines concurrently into the bloodstream, typically in response to infection or immune therapy.
- Drug repurposing
- a process of
References (15)
A review of cardiac glycosides: structure, toxicokinetics, clinical signs, diagnosis and antineoplastic potential
Toxicon
(2019)Digoxin suppresses pyruvate kinase M2-promoted HIF-1alpha transactivation in steatohepatitis
Cell Metab.
(2018)Cardiac glycoside digoxin ameliorates pro-inflammatory cytokines in PBMCs of rheumatoid arthritis patients in vitro
Int. Immunopharmacol.
(2020)Digoxin enhances the anticancer effect on non-small cell lung cancer while reducing the cardiotoxicity of Adriamycin
Front. Pharmacol.
(2020)- et al.
Na+/K+-ATPase as a signal transducer
Eur. J. Biochem.
(2002) - et al.
Current and future pharmacologic treatment of nonalcoholic steatohepatitis
Curr. Opin. Gastroenterol.
(2017) Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation
Am. J. Physiol. Gastrointest. Liver Physiol.
(2019)
Cited by (0)
- 4
These authors are co-first authors.