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A new subseries of ROMK inhibitors exemplified by 28 has been developed from the initial screening hit 1. The excellent selectivity for ROMK inhibition over related ion channels and pharmacokinetic properties across preclinical species support further preclinical evaluation of 28 as a new mechanism diuretic. Robust pharmacodynamic effects in both SD rats and dogs have been demonstrated.
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http://dx.doi.org/10.1021/ml500440u | DOI Listing |
Mol Divers
September 2025
Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, Nanjing, 211198, China.
Drug absorption significantly influences pharmacokinetics. Accurately predicting human oral bioavailability (HOB) is essential for optimizing drug candidates and improving clinical success rates. The traditional method based on experiment is a common way to obtain HOB, but the experimental method is time-consuming and costly.
View Article and Find Full Text PDFFood Sci Nutr
September 2025
Department of Nutrition Sciences, School of Health Larestan University of Medical Sciences Iran.
Chronic myeloid leukemia (CML), a myeloproliferative neoplasm, is characterized by the fusion gene, which results in constitutive tyrosine kinase activity. While tyrosine kinase inhibitors (TKIs) have significantly improved CML outcomes, resistance and the persistence of leukemic stem cells remain major clinical challenges. Curcumin, a natural polyphenol derived from , has demonstrated potential anticancer properties.
View Article and Find Full Text PDFFEBS Lett
September 2025
Laboratory of Molecular Diagnostics and Biotechnology, Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, Minsk, Belarus.
Genetic variants of various cytochrome P450 (CYP) enzymes significantly impact pharmacokinetics. The highly polymorphic hepatic CYP2C9 metabolizes ~ 15% of clinically used drugs. This study aimed to characterize the ligand-binding properties of the understudied CYP2C9.
View Article and Find Full Text PDFNat Commun
September 2025
Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China.
ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome is a rare genetic disease caused by variants in alpha-kinase 1 (ALPK1) resulting in downstream pro-inflammatory signaling mediated by the TIFA/TRAF6/NF-κB pathway. Here, we report the design of an ALPK1 inhibitor, DF-003, with pharmacokinetic properties suitable for daily oral dosing. In biochemical assays, DF-003 potently inhibits human ALPK1 (IC = 1.
View Article and Find Full Text PDFChem Res Toxicol
September 2025
C.F.E.B Sisley Paris, 32 Avenue des Béthunes, 95310 Saint Ouen L'Aumône, France.
The development of alternative methods to animal testing has gained momentum over the years, including the rapid growth of methods, which are faster and more cost-effective. A large number of tools have been published, focusing on Read-Across, (quantitative) Structure-Activity Relationship ((Q)SAR) models, and Physiologically Based Pharmacokinetic (PBPK) models. All of these methods play a crucial role in the risk assessment for cosmetics.
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