A5031697265- Venomous Animal Envenomation and Studies
- Ion channel regulation and function
- Insect and Pesticide Research
- Pneumocystis jirovecii pneumonia detection and treatment
- Antibiotic Resistance in Bacteria
- Pharmacogenetics and Drug Metabolism
- interferon and immune responses
- Analytical Chemistry and Chromatography
- Pluripotent Stem Cells Research
- Beetle Biology and Toxicology Studies
- Drug Transport and Resistance Mechanisms
- Cytokine Signaling Pathways and Interactions
- Synthesis and biological activity
- Cancer Cells and Metastasis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Toxin Mechanisms and Immunotoxins
- Alzheimer's disease research and treatments
- Chemical Reactions and Isotopes
- Platelet Disorders and Treatments
- Antibiotics Pharmacokinetics and Efficacy
- Nicotinic Acetylcholine Receptors Study
- Insect Resistance and Genetics
- 3D Printing in Biomedical Research
- Antimicrobial Peptides and Activities
- Mass Spectrometry Techniques and Applications
Shionogi (Japan)
2019-2025
Futaba (Japan)
2019-2021
Kyoto University
2011-2013
Abstract Drug absorption via the intestinal tissue is modulated by membrane permeability and metabolism in epithelial cells (IECs). In drug discovery research, using human IECs to evaluate metabolic stability can offer very useful information when exploring for candidate compounds that have good bioavailability trying predict fraction absorbed availability humans. Here, we evaluated pharmacokinetic functions of differentiated from induced pluripotent stem (hiPSCs) 3D cultures. As cultures...
Abstract Background COVID-19 caused by SARS-CoV-2 remains a global public health concern. Although oral direct-acting antivirals for (such as molnupiravir, nirmatrelvir/ritonavir, ensitrelvir) were approved clinical use, there are concerns about drug-drug interactions (DDI) and safety, so development of new therapeutics is needed. In this study, we describe enzyme inhibitory antiviral activity S-892216, second-generation small molecular 3C-like protease (3CLpro) inhibitor. Methods The 3CLpro...
Coadministration of β-lactam and β-lactamase inhibitor (BLI) is one the well-established therapeutic measures for bacterial infections caused by β-lactam-resistant Gram-negative bacteria, whereas we have only two options orally active BLI, clavulanic acid sulbactam. Furthermore, these BLIs are losing their clinical usefulness because spread new β-lactamases, including extended-spectrum β-lactamases (ESBLs) belonging to class A C D carbapenemases, which hardly or not inhibited classical BLIs....
Im-3 was isolated from the venom of scorpion Isometrus maculatus through several steps HPLC fractionation based on insect paralytic activity. Injecting into crickets induced paralysis, but no toxicity apparent in mice after an intracerebroventricular injection. shares sequence similarity to β-toxins that specifically affect sodium channels.
The β-site amyloid precursor protein cleaving enzyme 1 (BACE1, also known as β-secretase) is a promising target for the treatment of Alzheimer's disease. A pKa lowering approach over initial leads was adopted to mitigate hERG inhibition and P-gp efflux, leading design 6-CF3 dihydrothiazine 8 (N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-cyanopicolinamide). Optimization led discovery 15...
Scorpion venom is composed of a number peptides, many which show neurotoxicity. The Isometrus maculatus scorpion, belonging to the Buthidae family, found in tropical regions, including southern islands Japan, but there have been no reports on isolation toxins from its affecting sodium channels. We isolated this study novel toxin, Im-2, I. venom. Im-2 induced paralysis crickets after injecting 20 µg/g body weight. also lethality mice an intracerebroventricular injection, indicating that had...
By the emergence and worldwide spread of multi-drug-resistant Gram-negative bacteria, there have been growing demands for efficacious drugs to cure these resistant infections. The key mechanism resistance β-lactam antibiotics is production β-lactamases, which hydrolyze deactivate β-lactams. Diazabicyclooctane (DBO) analogs play an important role as one new classes β-lactamase inhibitors (BLIs), several compounds such avibactam (AVI) approved by FDA, along with many derivatives under clinical...
The human mass balance of lusutrombopag, an orally bioavailable thrombopoietin (TPO) receptor agonist, was characterised in seven healthy male subjects after a single oral dose [14C]-lusutrombopag (2 mg, 100 μCi) solution.Lusutrombopag the main component plasma, accounting for 56% plasma radioactivity AUC0-∞. In half-life (70.7 h) longer than that lusutrombopag (25.7 h), suggesting presence long circulating metabolites. excretion pathway lusutorombopag feces, with recovery approximately 83%...