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High potency 3-carboxy-2-methylbenzofuran pendrin inhibitors as novel diuretics.
Eur J Med Chem
December 2024
Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA. Electronic address:
Pendrin (SLC26A4) is an anion exchanger expressed in epithelial cells of kidney and lung. Pendrin inhibition is a potential treatment approach for edema, hypertension and inflammatory lung diseases. We have previously identified first-in-class pendrin inhibitors by high-throughput screening, albeit with low potency for pendrin inhibition (IC ∼10 μM).
View Article and Find Full Text PDFSacituzumab-govitecan-induced severe acute tubulointerstitial nephritis requiring hemodialysis.
BMC Nephrol
November 2024
Department of Medicine, Division of Oncology, Washington University in St. Louis, St. Louis, MO, USA.
Background: Sacituzumab govitecan is an antibody-drug conjugate that is FDA approved for refractory metastatic triple-negative breast cancer. It targets the human trophoblastic cell-surface antigen 2 (Trop-2) with SN-38, a topoisomerase I inhibitor, attached to the antibody [1]. SN-38 breaks DNA strands and induces tumor apoptosis [2].
View Article and Find Full Text PDF7-Hydroxycoumarin and its conjugated metabolites interact with organic anion transporters 1 and 3 in vitro and in vivo.
Chem Biol Interact
January 2025
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Drug Metabolism, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address:
7-Hydroxycoumarin (7-HC) is a natural coumarin compound rich in Chinese herbal medicines and has various pharmacological activities. After oral administration of 7-HC in rodents, its conjugated metabolites 7-hydroxycoumarin-β-D-glucuronide (7-HCG) and 7-hydroxycoumarin sulfate (7-HCS), exhibit high systemic exposure and urinary excretion. Organic anion transporters 1 and 3 (OAT1 and OAT3), mainly expressed in the proximal renal tubules, play an important role in drug-drug interactions and drug-induced kidney injury.
View Article and Find Full Text PDFThe deuterated pyrazoloquinolinone targeting α6 subunit-containing GABA receptor as novel candidate for inhibition of trigeminovascular system activation: implication for migraine therapy.
Front Pharmacol
August 2024
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Introduction: The α6 subunit-containing GABA receptors (α6GABARs) are highly expressed in the trigeminal ganglia (TG), the sensory hub of the trigeminovascular system (TGVS). Hypo-GABAergic transmission in the TG was reported to contribute to migraine-related behavioral and histopathological phenotypes. Previously, we found that Compound 6, an α6GABAR-selective positive allosteric modulator (PAM), significantly alleviated TGVS activation-induced peripheral and central sensitization in a capsaicin-induced migraine-mimicking model.
View Article and Find Full Text PDFInhibition of mTORC2 promotes natriuresis in Dahl salt-sensitive rats via the decrease of NCC and ENaC activity.
Am J Physiol Renal Physiol
September 2024
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Article Synopsis
- This study compares the effects of two mTOR inhibitors, rapamycin and PP242, on hypertension and kidney function in salt-sensitive rats.
- While rapamycin reduced hypertension and kidney inflammation, only PP242 completely prevented hypertension and improved kidney health, showing significant natriuretic effects.
- The research identified that PP242's natriuretic effect primarily results from inhibiting the Na-Cl cotransporter and reducing Na channel activity, suggesting it may be a better therapeutic option for managing blood pressure and kidney injury in salt-sensitive individuals.
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