Xanthenone based hydrazone derivatives (5a–n) have been synthesized as potential α-glucosidase inhibitors.
PBPK and its Virtual Populations: the Impact of Physiology on Pediatric Pharmacokinetic Predictions of Tramadol
In pediatric PBPK models, age-related changes in the body are known to occur.
Evaluation of blood-brain barrier penetration and examination of binding to human serum albumin of 7-O-arylpiperazinylcoumarins as potential antipsychotic agents
The delivery of drugs to the brain is complicated by the multiple factors including low blood–brain barrier (BBB) passive permeability, active BBB efflux systems, and plasma protein binding.
8-Hydroxy-2-(1H-1,2,3-triazol-1-yl)-1,4-naphtoquinone derivatives inhibited P2X7 Receptor-Induced dye uptake into murine Macrophages
Extracellular adenosine 5′-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1β cytokine into macrophages.
Computational Methods and Tools to Predict Cytochrome P450 Metabolism for Drug Discovery
In this review we present important, recent developments in the computational prediction of cytochrome P450 (CYP) metabolism in the context of drug discovery.
Physiologically based absorption modeling to predict bioequivalence of controlled release and immediate release oral products
Physiologically based absorption modeling was conducted to predict bioequivalence (BE) for immediate release (IR) and controlled release (CR) formulations.
Synthesis and Biological Evaluation of Novel Triple-Modified Colchicine Derivatives as Potent Tubulin-Targeting Anticancer Agents
Specific modifications of colchicine followed by synthesis of its analogues have been tested in vitro with the objective of lowering colchicine toxicity.
Tools and resources for metabolomics research community: A 2017–2018 update
The scale at which MS‐ and NMR‐based platforms generate metabolomics datasets for both research, core, and clinical facilities to address challenges in the various sciences—ranging from biomedical to agricultural—is underappreciated.
Bioequivalence comparison of pediatric Dasatinib formulations and elucidation of absorption mechanisms through integrated PBPK modeling
Sprycel® (Dasatinib) is a BCS II weakly basic drug that exhibits strong pH dependent solubility.
A Rapid Method to Estimate Hepatocyte Loss Due to Drug‐Induced Liver Injury
It is not currently possible to rapidly estimate the extent of hepatocyte loss during drug‐induced liver injury (DILI). We used a proprietary mechanistic model (DILIsym) to estimate percentage hepatocyte loss due...
Pharmacokinetics, tissue distribution and excretion of ACT001 in Sprague-Dawley rats and metabolism of ACT001
This study investigated pharmacokinetics, tissue distribution and excretion of ACT001 in Sprague-Dawley rats. Stability study and metabolism study of ACT001 are conducted.
In vitro and in vivo investigation of metabolic fate of riociguat by HPLC-Q-TOF/MS/MS and in silico evaluation of the metabolites by ADMET Predictor™
Riociguat, a guanyl cyclase inhibitor, is one of its kind drug regimen approved for management of pulmonary arterial hypertension and chronic thromboembolism pulmonary hypertension.
Integration of Precipitation Kinetics From an In vitro, Multicompartment Transfer System and Mechanistic Oral Absorption Modeling for Pharmacokinetic Prediction of Weakly Basic Drugs
Solubility, dissolution, and precipitation in the gastrointestinal tract can be critical for the oral bioavailability of weakly basic drugs.
Application of a Dynamic Fluid & pH Model to Simulate Intraluminal and Systemic Concentrations of a Weak Base in GastroPlus™
The application of preclinical in vitro and in silico models can help formulation scientists to predict the in vivo performance of a drug in an early stage of oral drug product development.
In Silico Simulation of Dissolution Profiles for Development of Extended-Release Doxazosin Tablets
Developing extended-release (ER) formulations with appropriate release characteristics can be challenging for formulation scientists.
Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective
Bile salt export pump (BSEP) inhibition has emerged as an important mechanism that may contribute to the initiation of human drug-induced liver injury (DILI).
Molecular Drivers of Crystallization Kinetics for Drugs in Supersaturated Aqueous Solutions
In this study, we explore molecular properties of importance in solution-mediated crystallization occurring in supersaturated aqueous drug solutions.
Using Quantitative Systems Toxicology to Investigate Observed Species Differences in CKA-Mediated Hepatotoxicity
CKA, a chemokine receptor antagonist intended for treating inflammatory conditions, produced dose-dependent hepatotoxicity in rats but advanced into the clinic where single doses of CKA up to 600 mg appeared safe in humans.
Drug discovery and computational strategies in the multitarget drugs era
The pharmaceutical industry is increasingly joining chemoinformatics in the search for the development of new drugs to be used in the treatment of diseases.
Nonclinical pharmacokinetics and in vitro metabolism of H3B-6545, a novel selective ERα covalent antagonist (SERCA)
H3B-6545, a novel selective estrogen receptor (ER)α covalent antagonist (SERCA) which inactivates both wild-type and mutant ERα, is in clinical development for the treatment of metastatic breast cancer.