A5079619553- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Pharmacological Effects and Toxicity Studies
- Cancer Immunotherapy and Biomarkers
- Drug-Induced Hepatotoxicity and Protection
- CAR-T cell therapy research
- Cancer Treatment and Pharmacology
- 3D Printing in Biomedical Research
- HIV/AIDS drug development and treatment
- Analytical Chemistry and Chromatography
- Mass Spectrometry Techniques and Applications
- Colorectal Cancer Treatments and Studies
- Immunotherapy and Immune Responses
- Lung Cancer Treatments and Mutations
- Estrogen and related hormone effects
- Metabolomics and Mass Spectrometry Studies
- Computational Drug Discovery Methods
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- Click Chemistry and Applications
- Sulfur Compounds in Biology
- Pesticide Residue Analysis and Safety
- Quinazolinone synthesis and applications
- Immune cells in cancer
- Radiopharmaceutical Chemistry and Applications
HiFiBiO Therapeutics (United States)
2021-2024
Wuhan Textile University
2024
Bristol-Myers Squibb (United States)
2013-2023
Neijiang Normal University
2021
Bristol-Myers Squibb (Germany)
2005-2020
BioMimetic Systems (United States)
2020
Princeton Public Schools
2020
Syngene International (India)
2017-2018
Biocon (India)
2017-2018
Bristol-Myers Squibb (India)
2017-2018
The programmed death protein (PD-1) and its ligand (PD-L1) play critical roles in a checkpoint pathway cancer cells exploit to evade the immune system. A same-day PET imaging agent for measuring PD-L1 status primary metastatic lesions could be important optimizing drug therapy. Herein, we have evaluated tumor targeting of an anti–PD-L1 adnectin after <sup>18</sup>F-fluorine labeling. <b>Methods:</b> An was labeled with <sup>18</sup>F 2 steps. This synthesis featured fluorination novel...
A sensitive and quantitative method was developed for the estimation of reactive metabolite formation in vitro. The utilizes reduced glutathione (GSH) labeled with a fluorescence tag as trapping agent fluorescent detection quantitation. derivatization GSH accomplished by reaction oxidized (GSSG) dansyl chloride to form dansylated GSSG. Subsequent reduction disulfide bond yielded (dGSH). Test compounds were incubated human liver microsomes presence dGSH NADPH, resulting mixtures analyzed HPLC...
The studies reported here were conducted to investigate the transport characteristics of apixaban (1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide) and understand impact transporters on distribution disposition. In human permeability glycoprotein (P-gp)- breast cancer resistance protein (BCRP)-cDNA–transfected cell monolayers as well Caco-2 monolayers, apparent efflux ratio basolateral-to-apical (<i>Pc</i><sub>B-A</sub>)...
Complex in vitro models (CIVM) offer the potential to improve pharmaceutical clinical drug attrition due safety and/ or efficacy concerns. For this technology have an impact, establishment of robust characterization and qualification plans constructed around specific contexts use (COU) is required. This article covers output from a workshop between Food Drug Administration (FDA) Innovation Quality Microphysiological Systems (IQ MPS) Affiliate. The intent was understand how CIVM technologies...
Abstract BACKGROUND Androgen receptor (AR) antagonists are part of the standard care for prostate cancer. Despite almost inevitable development resistance in tumors to AR antagonists, no new have been approved over a decade. Treatment failure is due mutations that increase activity response lower ligand concentrations as well result broader range ligands. The discover has occurred face continued research; enable progress, clear understanding reasons required. METHODS Non‐clinical drug safety...
Reactive metabolite formation has been associated with drug-induced liver, skin, and hematopoietic toxicity of many drugs that resulted in serious clinical toxicity, leading to development failure, black box warnings, or, some cases, withdrawal from the market. In vitro vivo screening for reactive proposed widely adopted pharmaceutical industry aim minimizing property thus risk (DIT). One most common methods is thiol trapping metabolites. Although it well-documented hepatotoxins form...
Tissue chips are poised to deliver a paradigm shift in drug discovery. By emulating human physiology, these have the potential increase predictive power of preclinical modeling, which turn will move pharmaceutical industry closer its aspiration clinically relevant and ultimately animal-free Despite tremendous science innovation invested tissue chips, significant challenges remain be addressed enable their routine adoption into industrial laboratory. This article describes main steps that...
Multiple endogenous compounds have been proposed as candidate biomarkers to monitor organic anion transporting polypeptide (OATP) function in preclinical species or humans. Previously, we demonstrated that coproporphyrins (CPs) I and III are appropriate clinical markers evaluate OATP inhibition recapitulate drug-drug interactions (DDIs). In the present study, investigated bile acids (BAs) dehydroepiandrosterone sulfate (DHEAS), hexadecanedioate (HDA), tetradecanedioate (TDA) plasma probes...
Plasma pyridoxic acid (PDA) and homovanillic (HVA) were recently identified as novel endogenous biomarkers of organic anion transporter (OAT) 1/3 function in monkeys. Consequently, this clinical study assessed the dynamic changes utility plasma PDA HVA an initial evaluation OAT1/3 inhibition early-phase drug development. The was designed a single-dose randomized, three-phase, crossover study; 14 Indian healthy volunteers received probenecid (PROB) (1000 mg orally) alone, furosemide (FSM) (40...
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...
Lysozyme, a common antimicrobial agent, is widely used in the food, biopharmaceutical, chemical, and medicine fields. Rapid effective isolation of lysozymes an everlasting topic. In this work, ethylene vinyl alcohol (EVOH) copolymer nanofibrous membranes with gradient porous structure for lysozyme adsorption were prepared through layer-by-layer nanofiber wet-laying cost-efficient ultraviolet (UV)-assisted graft-modification method, where benzophenone was as initiator...
Background: Some members of the arylamine family compounds, specifically 4-aminobiphenyl (ABP), 2-naphthylamine, and benzidine, are established human bladder carcinogens. Cigarette smoking use permanent hair dye contribute substantially to current exposure. Low levels 4-ABP exposure have been associated with non–smoking-related cancer. Other compounds coming from as yet unidentified environmental sources may also be Methods: We conducted a population-based case–control study in Los Angeles...
The covalent conjugation of polyethylene glycol (PEG, typical MW > 10k) to therapeutic peptides and proteins is a well-established approach improve their pharmacokinetic properties diminish the potential for immunogenicity. Even though PEG generally considered biologically inert safe in animals humans, slow clearance large PEGs raises concerns about adverse effects resulting from accumulation tissues following chronic administration, particularly central nervous system. key information...
Ixabepilone is the first epothilone to be approved for clinical use. Current data suggest epothilones have a role in treating taxane-resistant cancers and ixabepilone unaffected by at least some of mechanisms underlying chemoresistance. Here, we report series cytotoxicity transport studies assess potential P-glycoprotein (P-gp) breast cancer resistance protein (BCRP) resistance. A significant decrease ixabepilone-mediated was observed Madin-Darby canine kidney cells transfected with human...
BMS-641988 is an androgen receptor antagonist with increased potency relative to bicalutamide in both vitro and vivo prostate cancer models. A first-in-man phase I study was conducted define the safety tolerability of oral patients castration-resistant (CRPC).Doses were escalated from 5 150 mg based on discrete pharmacokinetic parameters cohorts three six subjects. After establishing 20 United States, a companion opened Japan assess differences drug metabolism between populations.Sixty-one...
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Co‐administration of gemfibrozil significantly increases the exposure repaglinide. CYP3A4 and CYP2C8 are important in metabolism OATP1B1 polymorphism is an independent predictor repaglinide pharmacokinetics. Gemfibrozil its O‐glucuronide inhibitors. STUDY ADDS Acyl glucuronidation a major metabolic pathway vitro . glucuronide inhibit UGT1A1 enzyme responsible for AIM To further explore mechanism underlying interaction between gemfibrozil, alone or...
The thiophene moiety has been recognized as a toxicophore because of the potential oxidative bioactivation leading to electrophilic species. introduction bulky or electron-withdrawing groups at α-carbon sulfur atom reduce eliminate bioactivation. In this article, we describe variety substituted thiophenes. These compounds were incubated in NADPH-fortified human liver microsomes with without addition reduced glutathione (GSH) trapping agent. resulting GSH adducts characterized by high...
Previously disclosed dihydropyrazolopyrimidines are potent and selective blockers of I(Kur) current. A potential liability with this chemotype is the formation a reactive metabolite which demonstrated covalent binding to protein in vitro. When substituted at 2 or 3 position, template yielded inhibitors, selectivity over hERG did not form metabolites. Subsequent optimization for potency PK properties lead discovery...