SGLT2 inhibition ameliorates nano plastics-induced premature endothelial senescence and dysfunction.

Nano plastics (NPs) have been a significant threat to human health and are known to cause premature endothelial senescence. Endothelial senescence is considered one of the primary risk factors contributing to numerous cardiovascular disorders. Recent studies have suggested that inhibition of sodium glucose co-transporter (SGLT2) ameliorates endothelial senescence and dysfunction.

Pharmacokinetics and Tissue Distribution of Enavogliflozin in Mice and Rats.

This study investigated the pharmacokinetics and tissue distribution of enavogliflozin, a novel sodium-glucose cotransporter 2 inhibitor that is currently in phase three clinical trials. Enavogliflozin showed dose-proportional pharmacokinetics following intravenous and oral administration (doses of 0.3, 1, and 3 mg/kg) in both mice and rats.

In Vitro Metabolism of DWP16001, a Novel Sodium-Glucose Cotransporter 2 Inhibitor, in Human and Animal Hepatocytes.

DWP16001 is currently in a phase 2 clinical trial as a novel anti-diabetes drug for the treatment of type 2 diabetes by selective inhibition of sodium-glucose cotransporter 2. This in vitro study was performed to compare the metabolism of DWP16001 in human, dog, monkey, mouse, and rat hepatocytes, and the drug-metabolizing enzymes responsible for the metabolism of DWP16001 were characterized using recombinant human cytochrome 450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes expressed from cDNAs. The hepatic extraction ratio of DWP16001 in five species ranged from 0.

Comparative Pharmacokinetics and Pharmacodynamics of a Novel Sodium-Glucose Cotransporter 2 Inhibitor, DWP16001, with Dapagliflozin and Ipragliflozin.

Since sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced blood glucose level by inhibiting renal tubular glucose reabsorption mediated by SGLT2, we aimed to investigate the pharmacokinetics and kidney distribution of DWP16001, a novel SGLT2 inhibitor, and to compare these properties with those of dapagliflozin and ipragliflozin, representative SGLT2 inhibitors. The plasma exposure of DWP16001 was comparable with that of ipragliflozin but higher than that of dapagliflozin. DWP16001 showed the highest kidney distribution among three SGLT2 inhibitors when expressed as an area under curve (AUC) ratio of kidney to plasma (85.

Anticancer activity of undecapeptide analogues derived from antimicrobial peptide, brevinin-1EMa.

In spite of great advances in cancer therapy, cancer remains the major cause of death throughout the world. The increasing resistance of cancer cells towards current anticancer drugs requires development of anticancer agents with a new mode of action. Some antimicrobial peptides have become therapeutic candidates as new anticancer agents.

Identification of a novel ubiquitin binding site of STAM1 VHS domain by NMR spectroscopy.

Interaction between the signal-transducing adapter molecule 1 (STAM1) Vps27/Hrs/Stam (VHS) domain and ubiquitin was investigated by nuclear magnetic resonance (NMR) spectroscopy. NMR evidence showed that the structure of STAM1 VHS domain resembles that of other VHS domains, especially the homologous domain of STAM2. We found that the VHS domain binds to ubiquitin via its hydrophobic patch consisting of N-terminus of helix 2 and C-terminus of helix 4 in which Trp26 on helix 2 plays a pivotal role in the binding.

Simultaneous determination of sildenafil and its active metabolite UK-103,320 in human plasma using liquid chromatography-tandem mass spectrometry.

A liquid chromatography-tandem mass spectrometric method for the simultaneous determination of sildenafil and its active N-demethylated metabolite, UK-103,320 in human plasma was developed. Sildenafil, UK-103,320 and the internal standard (DA-8159) were extracted from human plasma with dichloromethane at basic pH. A reverse-phase LC separation was performed on Luna phenylhexyl column with the mixture of acetonitrile-ammonium formate (10 mM, pH 6.