The computational chemistry and cheminformatics community faces many challenges to advancing the state of the art.
Effect of gastric pH on the pharmacokinetics of a BCS Class II compound in dogs: Utilization of an artificial stomach and duodenum dissolution model and GastroPlus™ simulations to predict absorption
Dogs are one of the most commonly used non-rodent species in toxicology studies and are known to have basal stomach pH ranging from 2 to 7 in the fasted state.
Application of PBPK modelling in drug discovery and development at Pfizer
Early prediction of human pharmacokinetics (PK) and drug–drug interactions (DDI) in drug discovery and development allows for more informed decision making.
The role of predictive biopharmaceutical modeling and simulation in drug development and regulatory evaluation
Advances in predicting in vivo performance of drug products has the potential to change how drug products are developed and reviewed.
A sequence within the varicella-zoster virus (VZV) OriS is a negative regulator of DNA replication and is bound by a protein complex containing the VZV ORF29 protein
The architecture of the varicella-zoster virus (VZV) origin of DNA replication (OriS) differs significantly from that of the herpes simplex virus (HSV) DNA replication origin.
Development of a physiologically based model for oseltamivir and simulation of pharmacokinetics in neonates and infants
Physiologically based pharmacokinetic (PBPK) modelling can assist in the development of drug therapies and regimens suitable for challenging patient populations such as very young children.
In Vitro and In Silico Strategies to Identify OATP1B1 Inhibitors and Predict Clinical Drug–Drug Interactions
To establish in vitro and in silico models that predict clinical drug–drug interactions (DDIs) with the OATP1B1 (SLCO1B1) transporter.
Selection of oral bioavailability enhancing formulations during drug discovery
The objective of this paper was to identify oral bioavailability enhancing approaches for a poorly water-soluble research compound during drug discovery stages using minimal amounts of material.
Pre-clinical and clinical pharmacokinetics of PF-02413873, a non-steroidal progesterone receptor antagonist
The recently discovered selective nonsteroidal progesterone receptor (PR) antagonist 4-[3-cyclopropyl-1-(methylsulfonylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy-2,6-dimethylbenzonitrile (PF-02413873)...
The Application of Physiologically Based Pharmacokinetic Modelling to Understanding the Clinical Pharmacokinetics of UK-369,003
5-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulfonyl)-pyridin-3-yl]-3-ethyl-2-(2-methoxy-ethyl)-2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one (UK-369,003) is a phosphodiesterase-5...
Physiological modeling and assessments of regional drug bioavailability of danoprevir to determine whether a controlled release formulation is feasible
Danoprevir, a potent, selective inhibitor of HCV NS3/4A protease, has a short half-life in humans. Therefore, the feasibility of a controlled release (CR) formulation to allow less frequent dosing...
Simulation of human intravenous and oral pharmacokinetics of 21 diverse compounds using physiologically based pharmacokinetic modelling
The importance of predicting human pharmacokinetics during compound selection has been recognized in the pharmaceutical industry. To this end there are many different approaches that are applied.
A Model of Threshold Behavior Reveals Rescue Mechanisms of Bystander Proteins in Conformational Diseases
Conformational diseases result from the failure of a specific protein to fold into its correct functional state. The misfolded proteins can lead to the toxic aggregation of proteins.
Black tea improves attention and self-reported alertness
Tea has previously been demonstrated to better help sustain alertness throughout the day in open-label studies.
Utility of Physiologically Based Absorption Modeling in Implementing Quality by Design in Drug Development
To implement Quality by Design (QbD) in drug development, scientists need tools that link drug products properties to in vivo performance
In Vitro-In Vivo Correlation for Gliclazide Immediate-Release Tablets Based on Mechanistic Absorption Simulation.
The aim of this study was to develop a drug-specific absorption model for gliclazide (GLK) using mechanistic gastrointestinal simulation technology (GIST) implemented...
Prediction of Oral Pharmacokinetics of cMet Kinase Inhibitors in Humans: Physiologically Based Pharmacokinetic Model versus Traditional One Compartment Model.
The objective of this study was to assess the physiologically based pharmacokinetic (PBPK) model for predicting plasma concentration-time profiles...
Use of structure-activity landscape index curves and curve integrals to evaluate the performance of multiple machine learning prediction models
Standard approaches to address the performance of predictive models that used common statistical measurements for the entire data set provide an overview of...
Pharmacokinetics of dietary cancer chemopreventive compound dibenzoylmethane in rats and the impact of nanoemulsion and genetic knockout of Nrf2 on its disposition
The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous...
Trends in kinase selectivity: insights for target class-focused library screening
A kinome-wide selectivity screen of >20000 compounds with a rich representation of many structural classes has been completed.