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Repurposing the Antidiabetic Drugs Glyburide, Gliquidone, and Glipizide in Combination with Benznidazole for Infection.
Pharmaceuticals (Basel)
December 2024
Department of Biochemistry, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Infection with the protozoan parasite causes human Chagas disease. Benznidazole (BNZ) and nifurtimox are the current drugs for the treatment; however, they induce severe adverse side effects in patients; therefore, there is a need to improve the treatment effectiveness and efficiency of these drugs for its safer use. : Glyburide, glipizide, and gliquidone, hypoglycemic drugs for diabetes treatment, were previously predicted to bind to dihydrofolate reductase-thymidylate synthase from by in silico docking analysis; they also showed antiproliferative effects against epimastigotes, the stage of the insect vector.
View Article and Find Full Text PDFTetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights.
Antibiotics (Basel)
January 2025
Department of Internal Medicine, School of Medicine, University of Split, 21000 Split, Croatia.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline and doxycycline, exhibit anti-inflammatory and immunomodulatory properties, making them potential supplementary treatments.
View Article and Find Full Text PDFDiscovery of the First Efficacious Adenosine 2A Receptor Negative Allosteric Modulators for High Adenosine Cancer Immunotherapies.
J Med Chem
January 2025
School of Pharmaceutical Sciences, University of Geneva, 1206 Geneva, Switzerland.
Inhibition of the adenosine 2A receptor (AR) is recognized as a promising immunotherapeutic strategy but is challenged by the ubiquity of AR function in the immune system. To develop a safe yet efficacious immunotherapy, the discovery of a novel negative allosteric modulator (NAM) was preferred. Leveraging an in-house, sensitive, high-throughput screening cellular assay, novel AR NAM scaffolds were identified, followed by an extensive structure-activity relationship (SAR) study, leading to the discovery of potent 2-amino-3,5-dicyanopyridine derivatives.
View Article and Find Full Text PDFProgress in the development of macrophage migration inhibitory factor small-molecule inhibitors.
Eur J Med Chem
January 2025
Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China; The State Key Laboratory of Southwestern Chinese Medicine Resources, Department of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Macrophage migration inhibitory factor (MIF) functions as a critical cytokine regulating inflammatory and immune responses. Extensive research has demonstrated its involvement in the progression of various cancers, autoimmune diseases, and inflammatory disorders, establishing it as a pivotal target for anti-inflammatory and anticancer interventions. Therapeutic strategies aimed at MIF primarily focus on suppressing its activity through small molecule inhibitors and natural compounds.
View Article and Find Full Text PDFTargeting Soluble Amyloid Oligomers in Alzheimer's Disease: A Hypothetical Model Study Comparing Intrathecal Pseudodelivery of mAbs Against Intravenous Administration.
Diseases
January 2025
Departamento de Medicina, Facultad de Ciencias de la Salud, Universidad de Oviedo, ES-33006 Oviedo, Spain.
Background/objective: Neurotoxic soluble amyloid-β (Aβ) oligomers are key drivers of Alzheimer's pathology, with evidence suggesting that early targeting of these soluble forms may slow disease progression. Traditional intravenous (IV) monoclonal antibodies (mAbs) face challenges, including limited brain penetration and risks such as amyloid-related imaging abnormalities (ARIA). This hypothetical study aimed to model amyloid dynamics in early-to-moderate Alzheimer's disease (AD) and compare the efficacy of IV mAn with intrathecal pseudodelivery, a novel method that confines mAbs in a subcutaneous reservoir for selective amyloid clearance in cerebrospinal fluid (CSF) without systemic exposure.
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