Current research leads to the assumption that drugs affecting more than one target could result in a more efficient treatment of diseases and fewer safety concerns. Administration of drugs inhibiting only one branch of the arachidonic acid cascade is usually accompanied by side effects. We therefore designed and synthesized a library of hybrid molecules incorporating an imidazo[1,2-a]pyridine and an urea moiety as novel soluble epoxide hydrolase (sEH)/5-lipoxygenase (5-LO) dual inhibitors. Evaluation of the compounds was accomplished by in vitro testing using recombinant enzyme assays.
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http://dx.doi.org/10.1021/jm301617j | DOI Listing |
Nanoscale
January 2025
Department of Biomedical Engineering, Sogang University, Seoul 04107, Korea.
The differentiation of human induced pluripotent stem cells (hiPSCs) into neural progenitor cells (NPCs) is a promising approach for the treatment of neurodegenerative diseases and regenerative medicine. Dual-SMAD inhibition using small molecules has been identified as a key strategy for directing the differentiation of hiPSCs into NPCs by regulating specific cell signaling pathways. However, conventional culture methods are time-consuming and exhibit low differentiation efficiency in neural differentiation.
View Article and Find Full Text PDFJpn J Clin Oncol
January 2025
Kindai University Hospital, 377-2 Onohigashi, Osakasayama, 589-8511, Osaka, Japan.
Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan).
Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off).
Bioorg Med Chem Lett
January 2025
National Taiwan University, School of Pharmacy, College of Medicine, Taipei 100 Taiwan. Electronic address:
Current CML treatments often suffer from undesired side effects. Herein we report the computation-assisted optimization of Bcr-Abl/C-Src dual kinase inhibitor. We surmised the improved toxicity profile was achieved via disrupted ligand-target binding.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N. Pine St., Baltimore, MD, 21201, USA; University of Maryland Marlene & Stewart Greenebaum Comprehensive Cancer Center, 22 S. Greene St., Baltimore, MD, 21201, USA. Electronic address:
Current treatments for acute myeloid leukemias (AMLs) cure fewer than 30 % of patients. This low efficacy is due, in part, to the inter-patient and intra-patient heterogeneity of AMLs; accordingly, all current AML treatment regimens involve drug combinations (polypharmacy). A recently-completed clinical trial in relapsed/refractory AML using a combination of two newer targeted antileukemics, the BCL-2 inhibitor venetoclax (VEN) plus the FLT3 inhibitor gilteritinib (GIL), yielded highly promising results for this two-drug polypharmacy combination.
View Article and Find Full Text PDFRev Med Suisse
January 2025
Service d'endocrinologie et diabétologie, Hôpitaux universitaires de Genève, 1211 Genève 14.
Diabetology is a continuously evolving discipline, many molecules are developed, and treatment recommendations change regularly according to the latest published studies. After lifestyle measures that must always be preferred before any drug, metformin remains the pharmacological basis of treatment. Current recommendations favor the introduction of an SGLT2 inhibitor or a GLP-1 receptor agonist after metformin because these molecules have shown beneficial cardiovascular and renal effects.
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