In silico and in vitro methods have emerged as valuable tools to rapidly screen and prioritize large numbers of chemicals including new drug entities, food ingredients, and environmental compounds for further in vivo analysis.
Model-based meta-analysis of relapsing mouse model studies from the critical path to tuberculosis drug regimens initiative database
erculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb), remains a leading infectious disease-related cause of death worldwide, necessitating the development of new
Molecular docking and pharmacokinetics studies of Curcuma longa (Curcumin) potency against Ebola virus
The Ebola virus disease causing hemorrhagic fever in human, has been known for nearly about 40 years, with the most recent outbreak being in West Africa creating...
Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria
A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay.
High-Throughput Screening for Extracellular Inhibitors of the FLT3 Receptor Tyrosine Kinase Reveals Chemically Diverse and Druggable Negative Allosteric Modulators
Inhibiting receptor tyrosine kinases is commonly achieved by two main strategies targeting either the intracellular kinase domain by low molecular weight compounds or...
In vivo neurophysiological assessment of in silico predictions of neurotoxicity: Citronellal, 3,4-dichloro-1-butene, and benzyl bromoacetate
Neurotoxicants may be widespread in the environment and can produce serious health impacts in the human population.
Clinical Pharmacokinetics and Pharmacodynamics of Esaxerenone, a Novel Mineralocorticoid Receptor Antagonist: A Review
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.