We sought to evaluate androgen receptor (AR) and PI3K pathway activity in ovarian cancer cell lines and tissue and determine if either pathway was correlated with growth...
Development of a Direct CD8+ T Cell Activation QSP Model for Ovalbumin in the Context of Liver Injury Advances Groundwork for Mathematical Representation of Idiosyncratic Drug-Induced Liver Injury (iDILI)
Extensive progress has been made in identifying mechanisms for dose-dependent drug-induced liver injury (DILI) and in developing screening assays to reduce its incidence.
In Silico and in Vitro Simulations to Predict Idiosyncratic DILI: What is on the Horizon?
Multiple species: human, rat, mouse, and dog, Population variability, The three primary acinar zones of liver represented, Essential cellular processes represented to multiple scales in interacting submodels...
Assessing and Managing DILI Risk in Trials: A Consultant’s Perspective
DILI typically has drug-specific “signatures”: Hepatocellular, cholestatic, mixed (R-value), Latency “window,” Rate of progression, rate of resolution, Extra-hepatic manifestations (e.g. hypersensitivity signs)
Assessing Effects of BHV-0223 40 mg Zydis® Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym®
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons that leads to progressive muscle weakness and difficulties in speaking, swallowing, and breathing.
In Silico Prediction of Plasma Concentrations of Fluconazole Capsules with Different Dissolution Profiles and Bioequivalence Study Using Population Simulation
A biowaiver is accepted by the Brazilian Health Surveillance Agency (ANVISA) for immediate-release solid oral products containing Biopharmaceutics Classification System (BCS) class I drugs showing rapid drug dissolution.
Minor structural modifications of bisphenol A strongly affect physiological responses of HepG2 cells
Bisphenols represent a large group of structurally similar compounds.
The Discriminatory Power of the BCS-based Biowaiver: A Retrospective with Focus on Essential Medicines
This article summarizes historic developments, recent expert opinions and (currently) unresolved challenges concerning the Biopharmaceutics Classification System (BCS) based biowaiver.
Analysis of pharmacological mechanisms and targets mining of Wuzi-Yanzong-Wan for treating non-obstructive oligoasthenospermia
As a classical traditional Chinese medicine, Wuzi-Yanzong-Wan (WZYZW) has been widely applied for several centuries to treat non-obstructive oligoasthenozoospermia (NOA), although its pharmacological mechanisms remain largely unknown.
Quantitative Analysis of Tozadenant Using Liquid Chromatography-Mass Spectrometric Method in Rat Plasma and Its Human Pharmacokinetics Prediction Using Physiologically Based Pharmacokinetic Modeling
Tozadenant is one of the selective adenosine A2a receptor antagonists with a potential to be a new Parkinson’s disease (PD) therapeutic drug. In this study, a liquid chromatography-massspectrometry ...
Cu-mediated synthesis of differentially substituted diazepines as AChE inhibitors; validation through molecular docking and Lipinski’s filter to develop novel anti-neurodegenerative drugs
A highly efficient Cu-mediated route for the synthesis of fused [1,2,3]triazolo[1,4]diazepines has been developed by azidation-cyclization of 2-bromo-N-propargylamines in a one-pot fashion.
Enabling Personalized Medicine Through Pharmacokientic Modeling
Personalized medicine strives to deliver the ‘right drug’ at the ‘right dose’ at the ‘right time’ by considering the unique characteristics that define specialized populations of patients and contribute to inter-individual variability...
GastroPlus® User Group Webinar: Applications/Experiences of PBPK Modeling to Support Regulatory Interactions
Recent experiences with PBPK model-based regulatory submissions used to obtain product development and DDI waivers will be discussed.
In silico methods for development of generic drug‐device combination orally inhaled drug products
Development of generic single‐entity drug‐device combination products for orally inhaled drug products (OIDPs) is challenging, due in part to the complex nature of device design characteristics, and to the...
Lisa LaVange, PhD, Appointed to Board of Directors of Simulations Plus
Brings 35+ Years of Industry and Regulatory Expertise to Board
Predicting pK a for Small Molecules on Public and In‐house Datasets Using Fast Prediction Methods Combined with Data Fusion
Data fusion approach was investigated in the context of pKa prediction for 391 small molecules derived from a public data source as well as for 681 compounds from an internal corporate database.
Calculating the Partition Coefficients of Organic Solvents in Octanol/Water and Octanol/Air
Partition coefficients define how a solute is distributed between two immiscible phases at equilibrium.
In-silico and In-vitro Drug Analysis of Selected Flavonoids, Including Fusarochromanone
In recent years, there has been a shift in the pre-clinical drug discovery paradigm from a strict in-vitro process toward an in-silico based process.
Supporting systems science through in silico applications: A focus on informing metabolic mechanisms
Despite the advent of new in silico methodologies to characterize exposure and pharmacokinetic properties of environmental chemicals, numerous limitations remain in the understanding and predicting of metabolic processes.
Properties of FDA-approved small molecule protein kinase inhibitors
Because mutations, overexpression, and dysregulation of protein kinases play essential roles in the pathogenesis of many illnesses, this enzyme family has become one of the most important drug targets in the past 20 years.