A5078250663- Pharmacogenetics and Drug Metabolism
- Sleep and Wakefulness Research
- Advanced Photocatalysis Techniques
- Sleep and related disorders
- Drug Transport and Resistance Mechanisms
- Circadian rhythm and melatonin
- Ammonia Synthesis and Nitrogen Reduction
- Inflammatory mediators and NSAID effects
- Hepatitis C virus research
- Pharmacological Effects and Toxicity Studies
- Analytical Chemistry and Chromatography
- Photochromic and Fluorescence Chemistry
- Metabolomics and Mass Spectrometry Studies
- Pesticide Exposure and Toxicity
- HIV/AIDS drug development and treatment
- Radioactive element chemistry and processing
- Quantum Dots Synthesis And Properties
- Chronic Myeloid Leukemia Treatments
- Eicosanoids and Hypertension Pharmacology
- Polyoxometalates: Synthesis and Applications
- Covalent Organic Framework Applications
- X-ray Diffraction in Crystallography
- Advanced Nanomaterials in Catalysis
- Cancer Treatment and Pharmacology
- Nanomaterials for catalytic reactions
Northeast Normal University
2022-2024
Krirk University
2022-2023
Beijing Research Institute of Mechanical and Electrical Technology
2023
Teva Pharmaceuticals (United States)
2018
Henan Agricultural University
2018
Takeda (United States)
2017
Merck & Co., Inc., Rahway, NJ, USA (United States)
2013-2016
United States Military Academy
1998-2015
Vertex Pharmaceuticals (United States)
2015
AstraZeneca (United States)
2015
Despite increased understanding of the biological basis for sleep control in brain, few novel mechanisms treatment insomnia have been identified recent years. One notable exception is inhibition excitatory neuropeptides orexins A and B by design orexin receptor antagonists. Herein, we describe how efforts to understand origin poor oral pharmacokinetics a leading HTS-derived diazepane antagonist led identification compound 10 with 7-methyl substitution on core. Though displayed good potency,...
Orexins/hypocretins are key neuropeptides responsible for regulating central arousal and reward circuits. Two receptors respond to orexin signaling, 1 receptor (OX(1)R) 2 (OX(2)R) with partially overlapping nervous system distributions. Genetic studies suggest antagonists could be therapeutic insomnia other disorders disruptions of sleep wake. Suvorexant (MK-4305) is a potent, selective, orally bioavailable antagonist OX(1)R OX(2)R currently under clinical investigation as novel therapy...
Raltegravir is a potent human immunodeficiency virus 1 (HIV-1) integrase strand transfer inhibitor that being developed as novel anti-AIDS drug. The absorption, metabolism, and excretion of raltegravir were studied in healthy volunteers after single oral dose 200 mg (200 microCi) [(14)C]raltegravir. Plasma, urine, fecal samples collected at specified intervals up to 240 h postdose, the analyzed for total radioactivity, parent compound, metabolites. Radioactivity was eliminated substantial...
SPRYCEL (dasatinib, BMS-354825; Bristol-Myers Squibb, Princeton, NJ), a multiple kinase inhibitor, is currently approved to treat chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic tumors in patients who are resistant or intolerant imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). After 100-mg single p.o. dose of [<sup>14</sup>C]dasatinib healthy volunteers, the radioactivity was rapidly absorbed (<i>T</i><sub>max</sub> ∼0.5 h). Both dasatinib...
Insomnia is a common disorder that can be comorbid with other physical and psychological illnesses. Traditional management of insomnia relies on general central nervous system (CNS) suppression using GABA modulators. Many these agents fail to meet patient needs respect sleep onset, maintenance, next-day residual effects have issues related tolerance, memory disturbances, balance. Orexin neuropeptides are regulators wakefulness, orexin antagonism has been identified as novel mechanism for...
Abstract Background Drugs targeting insomnia ideally promote sleep throughout the night, maintain normal architecture, and are devoid of residual effects associated with morning sedation. These features an ideal compound not only dependent upon pharmacokinetics, receptor binding kinetics, potency pharmacodynamic activity, but also a compound’s mechanism action. Results Dual orexin antagonists (DORAs) block arousal-promoting activity peptides and, as demonstrated in current work, exhibit...
Photocatalytic nitrogen fixation is one of the important pathways for green and sustainable ammonia synthesis, but extremely high bonding energy N≡N triple bond makes it difficult conventional photocatalysts to directly activate hydrogenate. Given this, we covalently grafted phenanthroline unit onto graphitic carbon nitride nanosheets (CN) by simple thermal oxidation method complexed with transition metal Fe3+ ions obtain stable dispersed Fe active sites, which can significantly improve...
To identify the cytochrome P450 (CYP) isoform(s) responsible for formation of primary metabolite ziprasidone (ziprasidone sulphoxide), to determine kinetics its and predict possible drug interactions by investigating CYP isoform inhibition in an vitro study.In metabolism [14C]-ziprasidone was studied using human liver microsomes. The metabolites were identified mass spectrometry. determined (10-200 microM) over 5 min, Km Vmax estimated from Lineweaver-Burk plots. IC50 values specific probe...
Abstract The field of small‐molecule orexin antagonist research has evolved rapidly in the last 15 years from discovery peptides to clinical proof‐of‐concept for treatment insomnia. Clinical programs have focused on development antagonists that reversibly block action endogenous at both 1 and 2 receptors (OX R OX R), termed dual receptor (DORAs), affording late‐stage candidates including Merck’s suvorexant (new drug application filed 2012). Full characterization pharmacology associated with...
Caspofungin acetate (MK-0991) is a semisynthetic pneumocandin derivative being developed as parenteral antifungal agent with broad-spectrum activity against systemic infections such those caused by Candida and Aspergillus species. Following 1-h i.v. infusion of 70 mg [(3)H]MK-0991 to healthy subjects, excretion drug-related material was very slow, that 41 35% the dosed radioactivity recovered in urine feces, respectively, over 27 days. Plasma samples collected around 24 h postdose contained...
[<sup>14</sup>C]Etoricoxib (100 μCi/dose) was administered to six healthy male subjects (i.v., 25 mg; p.o., 100 mg). Following the i.v. dose, plasma clearance 57 ml/min, and harmonic mean half-life 24.8 h. Etoricoxib accounted for majority of radioactivity (∼75%) present in following both p.o. doses. The oral as a solution polyethylene glycol-400, well absorbed (absolute bioavailability ∼83%). Total recovery excreta 90% (i.v.) 80% (p.o.), with 70% 60% (p.o.) excreted urine 20% feces after...
N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide (dasatinib, Sprycel, BMS-354825; Bristol-Myers Squibb, Princeton, NJ) is a potent protein kinase inhibitor to treat chronic myeloid leukemia. In vivo studies have shown that the primary oxidative metabolites of dasatinib are M4 (N-dealkylation), M5 (N-oxidation), M6 (carboxylic acid formation), M20, and M24 (hydroxylation). To identify enzymes responsible for formation...
The inhibitory effect of boceprevir (BOC), an inhibitor hepatitis C virus nonstructural protein 3 protease was evaluated in vitro against a panel drug-metabolizing enzymes and transporters. BOC, known substrate for cytochrome P450 (P450) CYP3A aldo-ketoreductases, reversible time-dependent (k(inact) = 0.12 minute(-1), K(I) 6.1 µM) CYP3A4/5 but not other major P450s, nor UDP-glucuronosyltransferases 1A1 2B7. BOC showed weak to no inhibition breast cancer resistance (BCRP), P-glycoprotein...
In this paper, we successfully prepared a Z-scheme Cu/WO 2 /C-BOB heterostructure with LSPR effect for efficient photocatalytic nitrogen fixation reaction, which provides new idea the study of plasma heterojunction photocatalysts.
In an effort to improve the efficiency of TSQ 7000 LC-MS/MS system for identification drug metabolites in biological matrices support discovery programs, a combination instrument control language procedures Finnigan MAT mass spectrometer, referred as INTAMS, were composed. INTAMS was designed conduct unattended, automatic liquid chromatography/mass spectrometry (LC-MS) and analyses drugs commonly encountered vitro matrices. A novel peak detection algorithm developed automatically detect...
Sulfation of ethinyl estradiol (EE) is a major pathway first pass metabolism in both the intestine and liver. Consequently, we sought to identify human sulfotransferases (SULTs) involved 3-<i>O</i>-sulfation EE (EE-SULT). Based on results described herein, cDNA-expressed cytosolic SULT1A3 SULT1E1 were identified as low <i>K</i><sub>m</sub> isoforms (18.9 6.7 nM, respectively) mediating sulfation EE. In contrast, EE-SULT catalyzed by other recombinant SULTs (SULT1A1 2A1) was relatively high...
Various groups have sought to determine the impact of CYP2C8 genotype (and inhibition) on pharmacokinetics (PK) ibuprofen (IBU) enantiomers. However, contribution cytochrome P450 2C8 (CYP2C8) in human liver microsomes (HLMs) has not been reported. Therefore, vitro (P450) reaction phenotyping was conducted with selective inhibitors 2C9 (CYP2C9) and CYP2C8. In presence HLMs, sulfaphenazole (CYP2C9 inhibitor), anti-CYP2C9 monoclonal antibodies (mAbs) inhibited (73-100%) 2- 3-hydroxylation both...
Recent European Medicines Agency (final) and US Food Drug Administration (draft) drug interaction guidances proposed that human circulating metabolites should be investigated in vitro for their drug-drug (DDI) potential if present at ≥ 25% of the parent area under time-concentration curve (AUC) (US Administration) or 10% total drug-related AUC (European Agency). To examine application these regulatory recommendations, a group scientists, representing 18 pharmaceutical companies Metabolism...
The g-C 3 N 4 @TiO 2 composite photoanode corresponding to the cell shows best photoelectric performance, with PCE=8.2%. Tg-C can inhibit “electron-hole” recombination, and high stability prolong service life of cell.