Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases
Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases.
Translational PK/PD modeling for cardiovascular safety assessment of drug candidates: Methods and examples in drug development
Cardiovascular toxicity is a significant cause of candidate failure in drug development. Pharmacokinetic/pharmacodynamic (PK/PD) modeling may reduce attrition by improving the understanding...
Testicular distribution and toxicity of a novel LTA4H inhibitor in rats
JNJ 40929837, a novel leukotriene A4 hydrolase inhibitor in drug development, was reported to induce testicular toxicity in rats.
Synthesis and in silico studies of pyrrolidine sulfonamide based dipeptides as ß-gluscosidase inhibitors
A series of novel pyrrolidine sulfonamide derivatives were designed, synthesized and screened in silico for their β-gluscosidase inhibitory activity.
Characterization of preclinical in vitro and in vivo ADME properties and prediction of human PK using a physiologically-based pharmacokinetic model for YQA-14, a new dopamine D3 receptor antagonist candidate for treatment of drug addiction
YQA-14 is a novel and selective dopamine D3 receptor antagonist, with potential for the treatment of drug addiction. However, earlier compounds in its structural class tend to have poor oral bioavailability.
Effects of novel cathepsin K inhibitor ONO-5334 on bone resorption markers: a study of four sustained release formulations with different pharmacokinetic patterns
The purpose of the study was clarify the effect of the cathepsin K inhibitor ONO 5334 on bone resortion markers using sustained release(SR) formulations with different pharmacokinetic (PK) patterns, and identify the optimal SR formulation.
Using beta binomials to estimate classification uncertainty for ensemble models
Quantitative structure-activity (QSAR) models have enormous potential for reducing drug discovery and development costs as well as the need for animal testing.
Synthesis and Antioxidant Activity Evaluation of New Compounds from Hydrazinecarbothioamide and 1,2,4-Triazole Class Containing Diarylsulfone and 2,4-Difluorophenyl Moieties
In the present investigation, new hydrazinecarbothioamides 4–6 were synthesized by reaction of 4-(4-X-phenylsulfonyl)benzoic acids hydrazides (X= H, Cl, Br) 1–3 with 2,4-difluorophenyl isothiocyanate and further...
The Biopharmaceutics Classification System: Subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC
The Biopharmaceutics Classification System (BCS) has found widespread utility in drug discovery, product development and drug product regulatory sciences.
PBPK models for the prediction of in vivo performance of oral dosage forms
Drug absorption from the gastrointestinal (GI) tract is a highly complex process dependent upon numerous factors including the physicochemical properties of the drug, characteristics of the...
Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals
A physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of flumioxazin, in the blood and fetus of pregnant humans during a theoretical accidental intake (1000mg/kg).
Non-linear assessment of anticancer activity of 17-picolyl and 17-picolinylidene androstane derivatives – Chemometric guidelines for further syntheses
The present paper deals with prediction of cytotoxic activity of 17-picolyl and 17-picolinylidene androstane derivatives toward androgen receptor negative prostate cancer cell line (PC-3).
Comparison of in silico models for prediction of Daphnia magna acute toxicity
Eight in silico modelling packages were evaluated and compared for the prediction of Daphnia magna acute toxicity from the viewpoint of the European legislation on chemicals, REACH.
Physiologically based pharmacokinetic modeling of CYP3A4 induction by rifampicin in human: influence of time between substrate and inducer administration
The induction of cytochrome P450 enzymes (CYPs) is an important source of drug-drug interaction (DDI) and can result in pronounced changes in pharmacokinetics (PK).
An evaluation of the potential for drug–drug interactions between bendamustine and rituximab in indolent nonHodgkin lymphoma and mantle cell lymphoma
Bendamustine plus rituximab has been reported to be effective in treating lymphoid malignancies.
Downregulation of IRF4 induces lytic reactivation of KSHV in primary effusion lymphoma cells
Primary effusion lymphoma (PEL), associated with the latent infection by KSHV, constitutively expresses interferon-regulatory factor 4 (IRF4).
Visualization and Communication of Pharmacometric Models With Berkeley Madonna
Population or other pharmacometric models are a useful means to describe, succinctly, the relationships between drug administration, exposure (concentration), and downstream changes in pharmacodynamic (PD) biomarkers and clinical endpoints, including the mixed effects of patient factors and random interpatient variation (fixed and random effects.
N-(furan-2-ylmethyl)-N-methylprop-2-yn-1-amine (F2MPA): A Potential Cognitive Enhancer with MAO Inhibitor Properties
A considerable body of human and animal experimental evidence links monoaminergic systems and cognition.
Simulation of the In Vivo Exposure to Ibuprofen Based on In Vitro Dissolution Profiles from Solid Dosage Forms
Four ibuprofen products in two or three concentrations of active pharmaceutical ingredient were evaluated in vitro, using the conditions recommended for the upper pH- value of the three stage dissolution testing.