A minireview on NHE1 inhibitors. A rediscovered hope in oncohematology.

6533b82dfe1ef96bd1291321

RESEARCH PRODUCT

A minireview on NHE1 inhibitors. A rediscovered hope in oncohematology.

subject

lovastatin lcsh:Medicine Apoptosis Pharmacology Guanidines Amiloride p-glycoprotein hemic and lymphatic diseases Drug Interactions Sulfones Cation Transport Proteins Sodium-Hydrogen Exchanger 1 leukemia Myeloid leukemia Hydrogen-Ion Concentration Sorafenib Up-Regulation Leukemia Leukemia Myeloid Acute Imatinib Mesylate Signal transduction Tyrosine kinase medicine.drug Signal Transduction Sorafenib Niacinamide isoprenylation Sodium-Hydrogen Exchangers bcr/abl Antineoplastic Agents Genes abl General Biochemistry Genetics and Molecular Biology statins Patents as Topic Cell Line Tumor Leukemia Myelogenous Chronic BCR-ABL Positive medicine Humans Protein Kinase Inhibitors cariporide na+/h+ exchanger Tumor hypoxia business.industry Phenylurea Compounds lcsh:R Osmolar Concentration intracellular ph medicine.disease Imatinib mesylate fms-Like Tyrosine Kinase 3 Fms-Like Tyrosine Kinase 3 Mutation Cancer research Tumor Hypoxia flt3/itd Hydroxymethylglutaryl-CoA Reductase Inhibitors business Heme Oxygenase-1 DNA Damage

description

Background: Na+/H+ exchanger-1 (NHE-1) is involved in pH regulation and is up-regulated in different malignancies. Activation of NHE-1 is one way for allowing cells to avoid intracellular acidification and protect them against apoptosis. Inhibitors of NHE-1 are able to decrease intracellular pH and induce apoptosis. Some statins can also act by partial inhibition of NHE-1. This review presents progress in understanding the mechanisms of action of these inhibitors, connections with certain genetic mutations and acquired treatment resistance, as well as new patents on them. Methods: A MEDLINE search for original and review articles using key terms, Na+/H+ exchanger, leukemia, cariporide, and amiloride. Recent patents with NHE-1 inhibitors published by United States Patent and Trademark Office are also presented. Results and Conclusions: Sorafenib is used for the treatment of acute myeloid leukemia patients carrying internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD) mutation. 5-(N, N-hexamethylene)-amiloride can increase the suppression of FLT3 signaling by sorafenib. NHE-1 inhibitors are able to increase the sensitivity of chronic myeloid leukemia cells to tyrosine kinase inhibitors, including through the inhibition of P-glycoprotein. NHE-1 inhibitors are promising adjuvant drugs for overcoming acquired resistance to treatment in various malignant hemopathies.

year	journal	country	edition	language
2015-12-03	Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia

10.5507/bp.2015.060 https://pubmed.ncbi.nlm.nih.gov/26725705