Quantitative predictions of pharmacokinetics (PKs) and concentration-time profiles using in vitro and in vivo preclinical data are critical to estimate systemic exposures for first-in-human studies.
Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm
Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development.
Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation
Amphetamine (AMP) salts-based extended-release (ER) drug products are widely used for the treatment of attention deficit hyperactivity disorder.
Discovery of new acetylcholinesterase inhibitors with small core structures through shape-based virtual screening
Targeting acetylcholinesterase (AChE) using small molecule inhibitors is considered to be the most successful therapeutic strategy in the treatment of Alzheimer’s disease (AD).
Prediction of pH dependent absorption using in vitro, in silico, and in vivo rat models: Early liability assessment during lead optimization
Weakly basic compounds which have pH dependent solubility are liable to exhibit pH dependent absorption. In some cases, a subtle change in gastric pH can significantly modulate the plasma concentration of...
In vitro dissolution methodology, mini-Gastrointestinal Simulator (mGIS), predicts better in vivo dissolution of a weak base drug, dasatinib
USP apparatus I and II are gold standard methodologies for determining the in vitro dissolution profiles of test drugs.
Intestinal solubility and absorption of poorly water soluble compounds: predictions, challenges and solutions
We have explored for which type of compounds biorelevant dissolution profiling in simulated intestinal fluids would accurately predict solubility in human intestinal fluid.
Development of a Physiologically Based Pharmacokinetic / Pharmacodynamic Model to Identify Mechanisms Contributing to Entacapone Low Bioavailability
Entacapone is an inhibitor of catechol-O-methyltransferase (COMT) and is being used to extend the therapeutic effect of levodopa in patients with advanced and fluctuating Parkinson's disease.
QSAR studies and design of new analogs of vitamin E with enhanced antiproliferative activity on MCF-7 breast cancer cells
Vitamin E is group of natural antioxidants comprised of tocopherols and tocotrienols.
Tales from the war on error: the art and science of curating QSAR data
Curating the data underlying quantitative structure–activity relationship models is a never-ending struggle. Some curation can now be automated but much cannot, especially where data as complex as...
TLR9-Targeted STAT3 Silencing Abrogates Immunosuppressive Activity of Myeloid-Derived Suppressor Cells from Prostate Cancer Patients
Purpose: Recent advances in immunotherapy of advanced human cancers underscored the need to address and eliminate tumor immune evasion. The myeloid-derived...
5-Aryl-1H-pyrazole-3-carboxylic acids as selective inhibitors of human carbonic anhydrases IX and XII
Inhibitory activity of a congeneric set of 23 phenyl-substituted 5-phenyl-pyrazole-3-carboxylic acids toward human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX and XII was evaluated by a stopped-flow CO2 hydrase assay.
Role of Self-Association and Supersaturation in Oral Absorption of a Poorly Soluble Weakly Basic Drug
Precipitation of weakly basic drugs in intestinal fluids can affect oral drug absorption.
Ranking the binding energies of p53 mutant activators and their ADMET properties
The guardian of the genome, p53, is the most mutated protein found in all cancer cells. Restoration of wild-type activity to mutant p53 offers promise to eradicate cancer cells using novel pharmacological agents.
Computational evidence to design an appropriate candidate for the treatment of Alzheimer’s disease through replacement of the heptamethylene linker of bis(7)tacrine with S-allylcysteine
Due to the multiple pathogens of Alzheimer's disease, multitarget-directed ligand (MTDL) design has been highly regarded in recent years.
Warfarin-dependent gamma-carboxylation regulates androgen receptor activity
The anti-coagulant warfarin prevents the gamma-carboxylation (gla) of target proteins by interfering with the vitamin K cycle through its inhibition of the vitamin K epoxide...
Role of computer-aided drug design in modern drug discovery
Drug discovery utilizes chemical biology and computational drug design approaches for the efficient identification and optimization of lead compounds.
Identification of Androgen Receptor Splice Variants in the Pten Deficient Murine Prostate Cancer Model
Androgen receptor (AR) variants are associated with resistance to anti androgen therapy both in human prostate cancer cell lines and clinical samples.
A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria
Malaria is one of the most significant causes of childhood mortality, but disease control efforts are threatened by resistance of the Plasmodium parasite to current therapies.
TLR9 signaling through NF-κB/RELA and STAT3 promotes tumor-propagating potential of prostate cancer cells
Prostate cancer progression was associated with tumorigenic signaling activated by proinflammatory mediators. However, the etiology of these events remains elusive.