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A group of clinically approved cancer therapeutic tyrosine kinase inhibitors was screened to test their effects on the expression of angiotensin-converting enzyme 2 (ACE2), the cell surface receptor for SARS-CoV-2. Here, we show that the receptor tyrosine kinase inhibitor imatinib (also known as STI571, Gleevec) can inhibit the expression of the endogenous ACE2 gene at both the transcript and protein levels. Treatment with imatinib resulted in inhibition of cell entry of the viral pseudoparticles (Vpps) in cell culture. In FVB mice orally fed imatinib, tissue expression of ACE2 was reduced, specifically in the lungs and renal tubules, but not in the parenchyma of other organs such as the heart and intestine. Our finding suggests that receptor tyrosine kinases play a role in COVID-19 infection and can be therapeutic targets with combined treatments of the best conventional care of COVID-19.
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http://dx.doi.org/10.3390/ijms22136938 | DOI Listing |
J Smooth Muscle Res
September 2025
Department of Physiology, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
Pulmonary arterial hypertension (PAH) is a rare and fatal cardiovascular disease characterized by pulmonary vascular remodeling, leading to a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure (PAP). Elevated PAP induces right ventricular hypertrophy and eventually progresses to right heart failure. Pulmonary vascular remodeling is primarily caused by the excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) in the medial layer.
View Article and Find Full Text PDFPLoS One
August 2025
Faculty of Medical Technology, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
Chronic myeloid leukemia (CML) is a hematologic malignancy originating from hematopoietic stem cells and driven by the BCR-ABL fusion oncogene. Imatinib (IM), a tyrosine kinase inhibitor, is commonly used as a frontline therapy for CML. However, some patients exhibit primary resistance or show persistent molecular evidence of disease despite treatment.
View Article and Find Full Text PDFSci Rep
August 2025
Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Approximately 1.5 million people worldwide suffer from chronic myeloid leukemia (CML). MicroRNAs (miRs) are important regulators of gene expression and offer an attractive option as biomarkers for cancer detection, diagnosis, and prognosis assessment in solid and liquid tumors.
View Article and Find Full Text PDFClin Transl Med
September 2025
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Background: Imatinib has been widely used in gastrointestinal stromal tumours and significantly improved the prognosis of GIST patients, but approximately half of patients develop acquired treatment resistance, highlighting the urgency for novel therapeutic strategies.
Methods: A variety of bioinformatic tools and laboratory experiments, RNA sequencing, animal models and the thermal proteome profiling assay were employed to validate our findings and investigate the antitumour effects of β-elemene.
Results: We found that imatinib-resistant GIST was associated with negative regulation of ferroptosis activity, and inducing ferroptosis can enhance the sensitivity of resistant cells to imatinib.
Curr Issues Mol Biol
August 2025
The Felsenstein Medical Research Center, Rabin Medical Center, Petah-Tikva 4941492, Israel.
Chronic myeloid leukemia (CML) results from the formation of the BCR-ABL1 chimeric protein which serves as a target for clinically used tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM). Although very efficient, the development of resistance to TKIs remains a critical issue for a subset of patients. In our study we aimed to identify one aspect of IM resistance in K-562 cells, a cell line used as a model for CML.
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