A5036472094- Metabolomics and Mass Spectrometry Studies
- Analytical Chemistry and Chromatography
- Liver Disease Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Metal complexes synthesis and properties
- DNA and Nucleic Acid Chemistry
- Microbial Metabolic Engineering and Bioproduction
- Pharmacogenetics and Drug Metabolism
- Molecular spectroscopy and chirality
- Drug Transport and Resistance Mechanisms
- Chemical Synthesis and Analysis
- Drug-Induced Hepatotoxicity and Protection
- NMR spectroscopy and applications
- Gut microbiota and health
- Protein Structure and Dynamics
- Ferrocene Chemistry and Applications
- Nitric Oxide and Endothelin Effects
- Electron Spin Resonance Studies
- Advanced Proteomics Techniques and Applications
- Biochemical and Molecular Research
- Advanced NMR Techniques and Applications
- Computational Drug Discovery Methods
- Protein purification and stability
- HIV/AIDS drug development and treatment
- Advanced Chemical Sensor Technologies
Pfizer (United States)
1993-2025
Bristol-Myers Squibb (United States)
2009-2020
University of Pittsburgh Medical Center
2015
Bristol-Myers Squibb (Germany)
2010-2014
Waters (United States)
2010
Imperial College London
2007-2010
Korea University
2009
Bristol-Myers Squibb (South Korea)
2009
Charles River Laboratories (United States)
2007
Pfizer (United Kingdom)
2007
Troglitazone (TGZ), the first glitazone used for treatment of type II diabetes mellitus and removed from market liver toxicity, was shown to bind covalently microsomal protein glutathione (GSH) following activation by cytochrome P450 (P450). The covalent binding <sup>14</sup>C-TGZ in dexamethasone-induced rat microsomes NADPH-dependent required active form P450; it completely inhibited ketoconazole (10 μM) GSH (4 mM). 3A4 Supersomes (9.2 nmol TGZ Eq/nmol P450) greater than that with 1A2...
A new peptide antagonist of voltage-activated calcium channels was purified from venom the funnel web spider, Agelenopsis aperta. This 48-amino acid peptide, omega-agatoxin (omega-Aga)-IVB, found to be a potent (Kd, approximately 3 nM) blocker P-type in rat cerebellar Purkinje neurons but had no activity against T-type, L-type, or N-type variety neurons. The channel-blocking properties omega-Aga-IVB were similar those another toxin, omega-Aga-IVA, which has 71% amino identity with...
We have developed an ultra performance liquid chromatography-mass spectrometry (UPLC-MS(E)) method to measure bile acids (BAs) reproducibly and reliably in biological fluids applied this approach for indications of hepatic damage experimental toxicity studies. BAs were extracted from serum using methanol, Acquity HSS column coupled a Q-ToF mass spectrometer was used separate identify 25 individual within 5 min. Employing gradient elution water acetonitrile over 21 min enabled the detection...
Immunotherapy has fundamentally changed the landscape of cancer treatment. Despite encouraging results with checkpoint modulators, response rates vary widely across tumor types, a majority patients exhibiting either primary resistance without significant initial to treatment or acquired subsequent disease progression. Hematopoietic progenitor kinase 1 (HPK1) is predominantly expressed in hematopoietic cell linages and serves as negative regulator T cells dendritic (DC). While HPK1 gene...
Perturbation of organic anion transporter (OAT) 1- and OAT3-mediated transport can alter the exposure, efficacy, safety drugs. Although there have been reports endogenous biomarkers for OAT1/3, none these all characteristics required a clinical useful biomarker. Cynomolgus monkeys were treated with intravenous probenecid (PROB) at dose 40 mg/kg in this study. As expected, PROB increased area under plasma concentration-time curve (AUC) coadministered furosemide, known substrate OAT1 OAT3, by...
The endothelins (ETs) are a family of bicyclic 21-amino acid peptides that potent and prolonged vasoconstrictors. It has been shown highly combined ETA/ETB receptor antagonists can be developed from the C-terminal hexapeptide ET (His16-Leu17-Asp18-Ile19-Ile20-Trp21), such as Ac-(D)Dip16-Leu-Asp-Ile-Ile-Trp21 (PD 142893) Ac-DBhg16-Leu-Asp-Ile-Ile-Trp21 145065). However, these compounds relatively unstable to enzymatic proteolysis determined in an vitro rat intestinal perfusate assay. This...
HIV nucleocapsid protein (NCp7) has been suggested as a possible target for 2,2'-dithiobis[benzamide] and benzisothiazolone agents that inhibit viral replication in infected cells (Rice et al. Science 1995, 270, 1194−1197). The solution behavior of these compounds the mechanistic events leading to removal Zn from vitro studied by electrospray ionization mass spectrometry, 500 MHz one- two-dimensional nuclear magnetic resonance spectroscopy, circular dichroism spectroscopy. We demonstrate (1)...
Genetic drift in animal populations has been a recognized concern for many years. Less understood is the potential phenotypic "drift" or variation that not related to any genetic change. Recently, stock Sprague-Dawley (Crl:CD(SD)) rats obtained from Charles River Raleigh facility demonstrated distinct endogenous urinary metabonomic profile differed historical control SD urine spectral profiles over past several years our laboratory. In follow-up studies, origin of variant phenotype was...
Acyl glucuronides have been implicated in the toxicity of many xenobiotics and marketed drugs. These toxicities are hypothesized to be a consequence covalent binding reactive forms acyl glucuronide proteins. Reactive intermediates arise from migration aglycone leading other positional stereoisomers under physiological conditions. In order screen for potential liabilities these metabolites during early phase pharmaceutical development, an NMR method based on disappearance anomeric resonance...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnti-Cancer platinum drug adducts with AMP: novel direct proton and platinum-195 NMR evidence for slowly interconverting "head-to-tail" rotamers. Potential role of amine ligand bulk NH groups in guanine selectivity anti-cancer activityMichael D. Reily Luigi G. MarzilliCite this: J. Am. Chem. Soc. 1986, 108, 21, 6785–6793Publication Date (Print):October 1, 1986Publication History Published online1 May 2002Published inissue 1 October...
A NMR spectroscopic method is described that enables the quantitation of specific lipid classes and components, independent fatty acid composition. We demonstrate this for measuring cholesterol, squalene, pools sterol esters, wax esters (WEs), triglyceride (TG) components in sebum meibum. When 600 MHz equipment used conjunction with highly sensitive cryogenically cooled probes, has adequate sensitivity, some applications, advantages over commonly HPLC-evaporative light-scattering detection...
1H NMR spectroscopy was used to investigate the metabolic effects of hepatotoxin galactosamine (galN) and mechanism by which glycine protects against such toxicity. Rats were acclimatized a 0 or 5% diet for 6 days subsequently administered vehicle, galN (500 mg/kg), (5% via diet), both glycine. Urine collected over 12 prior administration 24 hours thereafter. Serum liver tissue sampled on termination, post-dosing. The profiles biofluids tissues determined using high-field spectroscopy....
Objective Characteristic pathological changes define the progression of steatosis to nonalcoholic steatohepatitis (NASH) and are correlated metabolic pathways. A common rodent model NASH is methionine choline deficient (MCD) diet. The objective this study was perform full metabolomic analyses on liver samples determine which pathways altered most pronouncedly in condition humans, compare these models fatty disease (NAFLD). Methods principal component analysis for all 91 metabolites measured...