Amorphization is an attractive formulation technique for drugs suffering from poor aqueous solubility as a result of their high lattice energy.
RNA-seq reveals aurora kinase-driven mTOR pathway activation in patients with sarcomatoid metastatic renal cell carcinoma
Sarcomatoid metastatic renal cell carcinoma (mRCC) is associated with a poor prognosis, and the biology of the disease has been inadequately characterized.
Physiologically Based Absorption Modelling to Predict the Impact of Drug Properties on Pharmacokinetics of Bitopertin
Bitopertin (RG1678) is a glycine reuptake inhibitor in phase 3 trials for treatment of schizophrenia. Its clinical oral pharmacokinetics is sensitive to changes in drug substance particle size and dosage form.
Discovery of furan-2-carbohydrazides as orally active glucagon receptor antagonists
Furan-2-carbohydrazides were found as orally active glucagon receptor antagonists. Starting from the hit compound 5, we successfully determined the structure activity relationships of a series...
Network representations and methods for the analysis of chemical and biochemical pathways
Systems biologists increasingly use network representations to investigate biochemical pathways and their dynamic behaviours.
In Silico Prediction of Major Drug Clearance Pathways by Support Vector Machines with Feature-Selected Descriptors
We have previously established an in silico classification method ("CPathPred") to predict the major clearance pathways of drugs based on an empirical decision with only four physicochemical...
Dissolution testing combined with computer simulation technology to evaluate the bioequivalence of domestic amoxicillin capsule
Re-evaluation of bioequivalence of generic drugs is one of the key research focus currently. As a means to ensure consistency of the therapeutic effectiveness of drug products, clinical bioequivalence...
Intestinal transport of TRH analogs through PepT1: the role of in silico and in vitro modeling
The present study involves molecular docking, molecular dynamics (MD) simulation studies, and Caco-2 cell monolayer permeability assay to investigate the effect of structural modifications on...
Enhanced Solubility and Oral Bioavailability of y-Tocotrienol Using a Self-Emulsifying Drug Delivery System (SEDDS)
The aim of this study was to evaluate the in vitro and in vivo performance of γ-tocotrienol (γ-T3) incorporated in a self-emulsifying drugdelivery system (SEDDS)...
Design of a General-Purpose European Compound Screening Library for EU-OPENSCREEN
This work describes a collaborative effort to define and apply a protocol for the rational selection of a general-purpose screening library, to be used by the screening platforms affiliated with the EU-OPENSCREEN initiative.
Predicting when Biliary Excretion of Parent Drug is a Major Route of Elimination in Humans
Biliary excretion is an important route of elimination for many drugs, yet measuring the extent of biliary elimination is difficult, invasive, and variable.
Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid-Mediated DILI
Bile salt export pump (BSEP) inhibition has been proposed to be an important mechanism for drug-induced liver injury (DILI).
Maximum Entropy in Drug Discovery
Drug discovery applies multidisciplinary approaches either experimentally, computationally or both ways to identify lead compounds to treat various diseases.
Physiologically based pharmacokinetic modeling for assessing the clinical drug-drug interaction of alisporivir
Alisporivir is a novel cyclophilin-binding molecule with potent anti-hepatitis C virus (HCV) activity. In vitro data from human liver microsomes suggest that alisporivir is a substrate and a time-dependent inhibitor (TDI) of CYP3A4.
Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases
Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases.
Translational PK/PD modeling for cardiovascular safety assessment of drug candidates: Methods and examples in drug development
Cardiovascular toxicity is a significant cause of candidate failure in drug development. Pharmacokinetic/pharmacodynamic (PK/PD) modeling may reduce attrition by improving the understanding...
Testicular distribution and toxicity of a novel LTA4H inhibitor in rats
JNJ 40929837, a novel leukotriene A4 hydrolase inhibitor in drug development, was reported to induce testicular toxicity in rats.
Synthesis and in silico studies of pyrrolidine sulfonamide based dipeptides as ß-gluscosidase inhibitors
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.