High-throughput screening revealed diaryl pyrazole 3 as a selective albeit modest cholecystokinin 1 receptor (CCK1R) agonist. SAR studies led to the discovery and optimization of a novel class of 1,2-diaryl imidazole carboxamides. Compound 44, which was profiled extensively, showed good in vivo mouse gallbladder emptying (mGBE) and lean mouse overnight food intake (ONFI) reduction activities.
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http://dx.doi.org/10.1016/j.bmcl.2008.06.057 | DOI Listing |
Pharm Res
December 2024
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641Yamazaki, Noda-Shi, Chiba, 278-8510, Japan.
Purpose: Drug photodegradation is a matter of great concern because it can result in potency loss and adverse side effects. This study examines the light-induced degradation of dacarbazine catalyzed by vitamin B and flavin adenine dinucleotide (FAD) under light-emitting diode (LED) or fluorescent light irradiation.
Methods: Dacarbazine was irradiated with LED (405 nm) or fluorescent light in the presence of various equivalents of vitamin B or FAD.
J Med Chem
December 2024
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.
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December 2024
Department of Cardiovasology, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443002, China.
Objective: To investigate whether cardiac mast cells (MCs) participate in pressure overload-induced myocardial hypertrophy through the regulation of transient receptor potential vanilloid 4 (TRPV4).
Methods: Pressure overload-induced myocardial hypertrophy was induced via abdominal aortic constriction (AAC). Myocardial hypertrophy was evaluated by measuring the heart weight index (HW/BW), lung weight index (LW/BW), ratio of heart weight to tibia length (HW/TL), ratio of lung weight to tibia length (LW/TL), and cross-sectional area of myocardial cells.
Eur J Med Chem
November 2024
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 PDFFASEB J
December 2024
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Multiple signaling pathways have been reported to be altered in Myotonic Dystrophy type 1 (DM1) skeletal muscle, contributing to pathogenicity. In particular, previous work established that AMPK signaling, a key sensor of energy metabolism, is repressed in DM1 mouse muscle and that activating AMPK through exercise and/or with pharmacological activators is beneficial for the DM1 muscle phenotype. Here, we explored the effects of a newer, more specific allosteric AMPK activator acting directly on AMPK.
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