Esaxerenone is a selective, nonsteroidal, high-affinity mineralocorticoid receptor antagonist recently approved in Japan for the treatment of hypertension.
Potent Neutralization of Omicron and other SARS-CoV-2 Variants of Concern by Biparatopic Human VH Domains
The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics that are effective against a variety of strains of the virus.
Discovery of ASP5878: Synthesis and structure–activity relationships of pyrimidine derivatives as pan-FGFRs inhibitors with improved metabolic stability and suppressed hERG channel inhibitory activity
Fibroblast growth factor receptor 3 (FGFR3) is an attractive therapeutic target for the treatment of bladder cancer patients harboring genetic alterations in FGFR3.
Estrogenic Activity of Tetrazole Derivatives Bearing Bisphenol Structures: Computational Studies, Synthesis, and In Vitro Assessment
The classification of bisphenol A (BPA) as an industrial endocrine disruptor has led to a ban of this ubiquitous critical starting material from food and medical applications.
Predicting nonlinear relationships between external and internal concentrations with physiologically based pharmacokinetic modeling
Although external concentrations are more readily quantified and often used as the metric for regulating and mitigating exposures to environmental chemicals, the toxicological response to an environmental chemical is more directly related to its internal concentrations than the external concentration.
A biologically based model to quantitatively assess the role of the nuclear receptors liver X (LXR), and pregnane X (PXR) on chemically induced hepatic steatosis
Hepatic steatosis is characterized by the intracellular increase of free fatty acids (FFAs) in the form of triglycerides in hepatocytes.
Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, A Potential Oral Drug Candidate for COVID-19 Treatment
Preclinical pharmacokinetics (PK) and in vitro ADME properties of GS-441524, a potential oral agent for the treatment of Covid-19, were studied. GS-441524 was stable in vitro in liver microsomes, cytosols, and hepatocytes of mice, rats, monkeys, dogs, and humans.
Chlordecone: development of a physiologically based pharmacokinetic tool to support human health risks assessments
Chlordecone (CD; Kepone™) is a carcinogenic organochlorine insecticide with neurological, reproductive, and developmental toxicity that was widely used in the French West Indies (FWI) from 1973 to 1993 to fight banana weevils.
Synthesis and Characterization of Novel 2-Pyridine Mono(thio)carbohydrazones as Promising Antioxidant and Antimicrobial Agents. Experimental and Theoretical Approach
Four new derivatives of 2-pyridine mono(thio)carbohydrazones were synthesized by condensation of carbaldehydes with carbohydrazide and thiocarbohydrazide following a known procedure.
Applications of PBPK/PBBM modeling in generic product development: An industry perspective
Physiologically based pharmacokinetic (PBPK) modeling and physiologically based biopharmaceutics modeling (PBBM) are invaluable tools with wide applications during drug discovery and development stages.
Assessment of the predictive capability of modelling and simulation to determine bioequivalence of inhaled drugs: A systematic review
There are a multitude of different modelling techniques that have been used for inhaled drugs.
Alternative experimental approaches to reduce animal use in biomedical studies
We review experimental approaches that can be used instead of in vivo studies involving vertebrate animal models and human clinical trials.
Dose Number as a Tool to Guide Lead Optimization for Orally Bioavailable Compounds in Drug Discovery
Small molecule developability challenges have been well documented over the last two decades.
Predictive Performance of Next Generation Human Physiologically Based Kinetic (PBK) Models Based on In Vitro and In Silico Input Data
The goal of the present study was to assess the predictive performance of a generic human physiologically based kinetic (PBK) model based on in vitro and in silico input data and the effect of using different input approaches for chemical parameterization on those predictions.
In silico predictions of absorption of MDI substances after dermal or inhalation exposures to support a category based read-across assessment
Methylenediphenyl diisocyanate (MDI) substances used polyurethane production can range from their simplest monomeric forms (e.g., 4,4′-MDI) to mixtures of the monomers with various homologues, homopolymer, and prepolymer derivatives.
Preferential solvation study of (Z)-N-benzyl-2-{5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (3) in {NMP (1) + Water (2)} co-solvent mixture and GastroPlus software based in vitro simulation
(Z)-N-benzyl-2-{5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (3) (SE11) is a newly synthesized benzylidine thiazolidinedione to inhibit aldose reductase (AR) to control Diabetes Mellitus (DM) and related complications.
Dissolution Challenges Associated with the Surface pH of Drug Particles: Integration into Mechanistic Oral Absorption Modeling
The present work aimed to differentiate between in vitro dissolution profiles of ibuprofen as input for GastroPlus™ and to see the impact on systemic exposure.
Population Pharmacokinetic Modeling and Exposure-Response Analysis for Aripiprazole Once Monthly in Subjects With Schizophrenia
An intramuscular formulation of aripiprazole monohydrate dosed once monthly (AOM) was developed to address nonadherence with
Preferential Solvation Study of the Synthesized Aldose Reductase Inhibitor (SE415) in the {PEG 400 (1) + Water (2)} Cosolvent Mixture and GastroPlus-Based Prediction
(Z)-N-Benzyl-2-{2,4-dioxo-5-(4-prop-2-yl-1-yloxyl)benzylidene)thiazolin-3-yl)}acetamide (SE415) is a novel aldose reductase inhibitor used in the management of diabetes mellitus (DM) and associated complications.
In Vitro and In Silico Study of Analogs of Plant Product Plastoquinone to Be Effective in Colorectal Cancer Treatment
Plants have paved the way for the attainment of molecules with a wide-range of biological activities.