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.
Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs
During the last decades, the importance of modeling and simulation in clinical drug development, with the goal to qualitatively and quantitatively assess and understand mechanisms of pharmacokinetic processes...
Food Effect in Humans: Predicting the Risk Through In Vitro Dissolution and In Vivo Pharmacokinetic Models
In vitro and in vivo experimental models are frequently used to assess a new chemical entity's (NCE) biopharmaceutical performance risk for food effect (FE) in humans.
Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems
The objective of this study was to develop a level A in vitro-in vivo correlation (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermaldrug delivery systems (TDDS).
Implementing Toxicity Testing in the 21st Century (TT21C): Making safety decisions using toxicity pathways, and progress in a prototype risk assessment
Risk assessment methodologies in toxicology have remained largely unchanged for decades. The default approach uses high dose animal studies, together with human exposure estimates...
Marine Drug Discovery Database (MDDD) – A Database of In silico Predicted Physico-Chemical, Drug Likeness and Toxicological Properties of Marine Compounds
Marine is one of the largest and richest natural resources of bioactive compounds.
Predicting the extent of metabolism using in vitro permeability rate measurements and in silico permeability rate predictions
The Biopharmaceutics Drug Disposition Classification System (BDDCS) can be utilized to predict drug disposition, including interactions with other drugs and transporter or metabolizing enzyme effects based...