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.
In silico design, synthesis, & testing of Cyclooxygenase (COX) inhibitors
Following the success of our earlier NCE project, which focused on the design of antimalarial molecules, we sought to utilize our ADMET Design Suite™ to design novel compounds that inhibit both...
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.
GastroPlus™ Modeling Common Ion Effects and Enabled Formulations
Predictive mechanistic simulation of gastric dissolution and in vivo supersaturation and precipitation during oral absorption, using experimental parameters derived from in vitro measurements.
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).
KIWI: A Collaborative Platform for Modeling and Simulation
Drug development programs rely increasingly on pharmacometric analysis to support decision-making and submissions to regulatory agencies.1,2 To ensure high quality analysis, organizations must apply…
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.
Simulations Plus Reports Preliminary Revenues for Third Fiscal Quarter FY2014
New All-time Record Revenues in Third Quarter
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.
Simulations Plus Releases ADMET Predictor Version 7.0
Major upgrade improves all predictions, adds new ones
Simulations Plus Releases MedChem Studio Version 4.0 and MedChem Designer 3.0
Upgrades include powerful new optical structure recognition feature