Non-cancer to anti-cancer: investigation of human ether-a-go-go-related gene potassium channel inhibitors as potential therapeutics

Background The expression of hERG K.sup.+ channels is observed in various cancer cells including epithelial, neuronal, leukemic, and connective tissue. The role of hERG potassium channels in regulating the growth and death of cancer cells include cell proliferation, survival, secretion of proangioge...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Egyptian National Cancer Institute 2021-11, Vol.33 (1), p.1-16
Main Authors: Patil, Vaishali M, Gaurav, Anand, Garg, Priyanka, Masand, Neeraj
Format: Article
Language:English
Subjects:
Anti-cancer agents
Apoptosis
Cancer
Cardiac arrhythmia
Cardiotoxicity
Care and treatment
Cell cycle
Cell growth
Datasets
Diabetes
Dofetilide
Drug repurposing
Drug therapy
FDA approval
Genetic aspects
Genetic research
hERG inhibitors
Hypoglycemic agents
Investigations
Leukemia
Molecular docking
Non-cancer
Oncology, Experimental
Potassium
Potassium channels
Prevention
Thioridazine
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background The expression of hERG K.sup.+ channels is observed in various cancer cells including epithelial, neuronal, leukemic, and connective tissue. The role of hERG potassium channels in regulating the growth and death of cancer cells include cell proliferation, survival, secretion of proangiogenic factors, invasiveness, and metastasis. Methods In the reported study, an attempt has been made to investigate some non-cancer hERG blockers as potential cancer therapeutics using a computational drug repurposing strategy. Preliminary investigation for hERG blockers/non-blockers has identified 26 potential clinically approved compounds for further studies using molecular modeling. Results The interactions at the binding pockets have been investigated along with the prioritization based on the binding score. Some of the identified potential hERG inhibitors, i.e., Bromocriptine, Darglitazone, and Troglitazone, have been investigated to derive the mechanism of cancer inhibition. Conclusions The proposed mechanism for anti-cancer properties via hERG blocking for some of the potential compounds is required to be explored using other experimental methodologies. The drug repurposing approach applied to investigate anti-cancer therapeutics may direct to provide a therapeutic solution to late-stage cancer and benefit a significant population of patients.
ISSN:1110-0362
2589-0409
DOI:10.1186/s43046-021-00091-3