Specific modifications of colchicine followed by synthesis of its analogues have been tested in vitro with the objective of lowering colchicine toxicity.
Tools and resources for metabolomics research community: A 2017–2018 update
The scale at which MS‐ and NMR‐based platforms generate metabolomics datasets for both research, core, and clinical facilities to address challenges in the various sciences—ranging from biomedical to agricultural—is underappreciated.
Bioequivalence comparison of pediatric Dasatinib formulations and elucidation of absorption mechanisms through integrated PBPK modeling
Sprycel® (Dasatinib) is a BCS II weakly basic drug that exhibits strong pH dependent solubility.
A Rapid Method to Estimate Hepatocyte Loss Due to Drug‐Induced Liver Injury
It is not currently possible to rapidly estimate the extent of hepatocyte loss during drug‐induced liver injury (DILI). We used a proprietary mechanistic model (DILIsym) to estimate percentage hepatocyte loss due...
Pharmacokinetics, tissue distribution and excretion of ACT001 in Sprague-Dawley rats and metabolism of ACT001
This study investigated pharmacokinetics, tissue distribution and excretion of ACT001 in Sprague-Dawley rats. Stability study and metabolism study of ACT001 are conducted.
In vitro and in vivo investigation of metabolic fate of riociguat by HPLC-Q-TOF/MS/MS and in silico evaluation of the metabolites by ADMET Predictor™
Riociguat, a guanyl cyclase inhibitor, is one of its kind drug regimen approved for management of pulmonary arterial hypertension and chronic thromboembolism pulmonary hypertension.
Integration of Precipitation Kinetics From an In vitro, Multicompartment Transfer System and Mechanistic Oral Absorption Modeling for Pharmacokinetic Prediction of Weakly Basic Drugs
Solubility, dissolution, and precipitation in the gastrointestinal tract can be critical for the oral bioavailability of weakly basic drugs.
Application of a Dynamic Fluid & pH Model to Simulate Intraluminal and Systemic Concentrations of a Weak Base in GastroPlus™
The application of preclinical in vitro and in silico models can help formulation scientists to predict the in vivo performance of a drug in an early stage of oral drug product development.
In Silico Simulation of Dissolution Profiles for Development of Extended-Release Doxazosin Tablets
Developing extended-release (ER) formulations with appropriate release characteristics can be challenging for formulation scientists.
Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective
Bile salt export pump (BSEP) inhibition has emerged as an important mechanism that may contribute to the initiation of human drug-induced liver injury (DILI).
Molecular Drivers of Crystallization Kinetics for Drugs in Supersaturated Aqueous Solutions
In this study, we explore molecular properties of importance in solution-mediated crystallization occurring in supersaturated aqueous drug solutions.
Using Quantitative Systems Toxicology to Investigate Observed Species Differences in CKA-Mediated Hepatotoxicity
CKA, a chemokine receptor antagonist intended for treating inflammatory conditions, produced dose-dependent hepatotoxicity in rats but advanced into the clinic where single doses of CKA up to 600 mg appeared safe in humans.
Drug discovery and computational strategies in the multitarget drugs era
The pharmaceutical industry is increasingly joining chemoinformatics in the search for the development of new drugs to be used in the treatment of diseases.
Nonclinical pharmacokinetics and in vitro metabolism of H3B-6545, a novel selective ERα covalent antagonist (SERCA)
H3B-6545, a novel selective estrogen receptor (ER)α covalent antagonist (SERCA) which inactivates both wild-type and mutant ERα, is in clinical development for the treatment of metastatic breast cancer.
Second generation of diazachrysenes: Protection of Ebola virus infected mice and mechanism of action
Ebola virus (EBOV) causes a deadly hemorrhagic fever in humans and non-human primates.
Synthesis, Molecular Docking, and Antimycotic Evaluation of Some 3-Acyl Imidazo[1,2-a]pyrimidines
A series of 3-benzoyl imidazo[1,2-a]pyrimidines, obtained from N-heteroarylformamidines in good yields, was tested in silico and in vitro for binding and inhibition of seven Candida species...
Application of in silico Tools in Clinical Practice using Ketoconazole as a Model Drug
Hypochlorhydria is a condition where the production of hydrochloric acid in the stomach is decreased. As a result, the intragastric pH is elevated.
Prediction of ARA/PPI Drug-Drug Interactions at the Drug Discovery and Development Interface
Advances in understanding of human disease has prompted the Food and Drug Administration to classify certain molecules as “break-through therapies”, providing an accelerated review...
ETCM: an encyclopaedia of traditional Chinese medicine
Traditional Chinese medicine (TCM) is not only an effective solution for primary health care, but also a great resource for drug innovation and discovery.
Data Standards for Model-Informed Drug Development: an ISoP Initiative
Analysis datasets are fundamental components of pharmacometric analyses and their quality and readiness highly correlate with