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Improving Affinity while Reducing Kidney Uptake of CXCR4-Targeting Radioligands Derived from the Endogenous Antagonist EPI-X4.
ChemMedChem
January 2025
Universitatsspital Basel, Radiopharmazeutische Chemie, Petersgraben 4, 4031, Basel, SWITZERLAND.
The C-X-C chemokine receptor 4 (CXCR4) is highly upregulated in most cancers, making it an ideal target for delivering radiation therapy to tumors. We previously demonstrated the feasibility of targeting CXCR4 in vivo using a radiolabeled derivative of EPI-X4, an endogenous CXCR4 antagonist, named DOTA-K-JM#173. However, this derivative showed undesirable accumulation in the kidneys, which would limit its clinical use.
View Article and Find Full Text PDFClinical implications of mineralocorticoid receptor overactivation.
Clin Kidney J
January 2025
Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
The mineralocorticoid receptor (MR) is a nuclear transcription factor that plays a critical role in regulating fluid, electrolytes, blood pressure, and hemodynamic stability. In conditions such as chronic kidney disease (CKD) and heart failure (HF), MR overactivation leads to increased salt and water retention, inflammatory and fibrotic gene expression, and organ injury. The MR is essential for transcriptional regulation and is implicated in metabolic, proinflammatory, and pro-fibrotic pathways.
View Article and Find Full Text PDFTigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization.
J Inflamm Res
January 2025
Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People's Republic of China.
Purpose: Serum uric acid (SUA) is primarily produced through the hydrolysis of purines in the liver, with its excretion largely handled by the kidneys. Urate transporter 1 (URAT1) inhibitors are known to enhance uric acid elimination via the kidneys, but they also increase the risk of kidney stone formation. Currently, xanthine oxidase (XO) inhibitors are the predominant uric-lowering medications on the market.
View Article and Find Full Text PDF[Effects of high salt diet on renal vascular reactivity in mice detected by laser speckle contrast imaging].
Sheng Li Xue Bao
December 2024
Department of Physiology, Zhuhai Campus of Zunyi Medical University, Zhuhai 519040, China.
The aim of this study was to conduct experiments using laser speckle contrast imaging (LSCI) technology to investigate the effects of high salt diet on renal vascular reactivity in mice. LSCI is a technology for monitoring blood flow based on the laser speckle principle. It has been widely used to detect microcirculatory functions in tissues such as the skin and brain.
View Article and Find Full Text PDFPharmacokinetics, mass balance, and metabolism of [C]PLB1004, a selective and irreversible EGFR-TKI in humans.
Cancer Chemother Pharmacol
January 2025
Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, 250014, China.
Purpose: PLB1004, developed by Beijing Avistone Biotechnology Co., Ltd., is a safe, highly selective, and efficient irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) employed in treating non-small-cell-lung-cancer (NSCLC).
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