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Eradication of Therapy-Resistant Cancer Stem Cells by Novel Telmisartan Derivatives.
J Med Chem
January 2025
Department of Internal Medicine V, Hematology and Oncology, Tyrolean Cancer Research Institute (TKFI), Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck 6020, Austria.
The present structure-activity relationship study investigates the development of novel chemosensitizers targeting therapy-resistant cancer stem cells (CSCs). We used 4'-((2-propyl-1-benzo[]imidazole-1-yl)methyl)-[1,1'-biphenyl]-2-carboxylic acid, derived from the angiotensin II type 1 receptor blocker telmisartan, as a lead structure, demonstrating that the biphenyl moiety is essential for chemosensitizing activity. Introducing a methyl carboxylate or carboxamide instead of the COOH-group significantly enhanced this effect, leading to the development of highly potent compounds.
View Article and Find Full Text PDFCircumventing Imatinib resistance in CML: Novel Telmisartan-based cell death modulators with improved activity and stability.
Eur J Med Chem
February 2025
Department of Internal Medicine V, Hematology and Oncology, Tyrolean Cancer Research Institute (TKFI), Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address:
Drug resistance presents a significant challenge in cancer therapy, which has led to intensive research in resistance mechanisms and new therapeutic strategies. In chronic myeloid leukemia (CML), the introduction of Imatinib, the first tyrosine kinase inhibitor (TKI), drastically changed the outcome for patients. However, complete remission still cannot be achieved in a large number of patients in the long term.
View Article and Find Full Text PDFBackground: Genetic association studies can reveal biology and treatment targets but have received limited attention for stroke recovery. STRONG (Stroke, Stress, Rehabilitation, and Genetics) was a prospective, longitudinal (1-year), genetic study in adults with stroke at 28 US stroke centers. The primary aim was to examine the association that candidate genetic variants have with (1) motor/functional outcomes and (2) stress-related outcomes.
View Article and Find Full Text PDFEffects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats.
J Huntingtons Dis
April 2024
Department of Biology, Whitworth University, Spokane, WA, USA.
Background: Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction caused by a mutant huntingtin protein. Compromised metabolic activity resulting from systemic administration of the mitochondrial toxin, 3-nitropropionic acid (3-NP), is known to mimic the pathology of HD and induce HD-like symptoms in rats. N-hexanoic-Tyr-Ile-(6)-amino hexanoic amide (PNB-0408), also known as Dihexa, has been shown to have neuroprotective and procognitive properties in animal models of Alzheimer's and Parkinson's diseases.
View Article and Find Full Text PDFPNA6, a Lactosyl Analogue of Angiotensin-(1-7), Reverses Pain Induced in Murine Models of Inflammation, Chemotherapy-Induced Peripheral Neuropathy, and Metastatic Bone Disease.
Int J Mol Sci
October 2023
Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85721, USA.
Pain is the most significant impairment and debilitating challenge for patients with bone metastasis. Therefore, the primary objective of current therapy is to mitigate and prevent the persistence of pain. Thus, cancer-induced bone pain is described as a multifaceted form of discomfort encompassing both inflammatory and neuropathic elements.
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