The screening of chemical libraries with traditional methods, such as high-throughput screening (HTS), is expensive and time consuming.
Modeling ADMET
Drug discovery and development is a costly and time-consuming endeavor (Calcoen et al. Nat Rev Drug Discov 14(3):161–162, 2015; The truly staggering cost of inventing new drugs
In Silico Models for Acute Systemic Toxicity
In this chapter, we give an overview of the regulatory requirements for acute systemic toxicity information in the European Union, and we review the availability of structure-based computational models...
In Silico Prediction of Chemically Induced Mutagenicity: How to Use QSAR Models and Interpret Their Results
Information on genotoxicity is an essential piece of information gathering for a comprehensive toxicological characterization of chemicals.
Design, Synthesis, and Biological Evaluation of Novel PARP-1 Inhibitors Based on a 1H-Thieno[3,4-d] Imidazole-4-Carboxamide Scaffold
A series of poly(ADP-ribose)polymerase (PARP)-1 inhibitors containing a novel scaffold, the 1H-thieno[3,4-d]imidazole-4-carboxamide moiety, was designed and synthesized.
Novel S1P1 receptor agonists – Part 5: From amino-to alkoxy-pyridines
In a previous communication we reported on the discovery of aminopyridine 1as a potent, selective and orally active S1P1 receptor agonist.
Toward Biopredictive Dissolution for Enteric Coated Dosage Forms
The aim of this work was to develop a phosphate buffer based dissolution method for enteric-coated formulations with improved biopredictivity for fasted conditions.
In silico modeling of gastrointestinal drug absorption: predictive performance of three physiologically based absorption models
Gastrointestinal (GI) drug absorption is a complex process determined by formulation, physicochemical and biopharmaceutical factors, and GI physiology.
The solubility-permeability interplay and oral drug formulation design: Two heads are better than one
Poor aqueous solubility is a major challenge in today's biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect...
BDDCS, the Rule of 5 and drugability
The Rule of 5 methodology appears to be as useful today in defining drugability as when it was proposed, but recognizing that the database that we used includes only drugs that successfully reached the market.
Computational prediction of formulation strategies for beyond-rule-of-5 compounds
The physicochemical properties of some contemporary drug candidates are moving towards higher molecular weight, and coincidentally also higher lipophilicity in the quest for biological selectivity and specificity.
Characterizing the Dissolution Profiles of Supersaturable Salts, Cocrystals, and Solvates to Enhance In Vivo Oral Absorption
The purposes of this study were to elucidate the type-specific characteristics of salt, cocrystal, and solvate formulations upon dissolution and precipitation, and to clarify their effect on enhancing oral absorption.
LC-ESI-MS/MS estimation of loratadine-loaded self-nanoemulsifying drug delivery systems in rat plasma: Pharmacokinetic evaluation and computer simulations by GastroPlus™
A rapid, sensitive, and accurate bioanalytical method was established for the quantitation and pharmacokinetic investigation of loratadine (LTD) in rat plasma by liquid chromatography–electrospray ionization...
Methodology of oral formulation selection in the pharmaceutical industry
Pharmaceutical formulations have to fulfil various requirements with respect to their intended use, either in the development phase or as a commercial product.
Quantitative aspects of drug permeation across in vitro and in vivo barriers
The kinetics of permeation across epithelial and endothelial cell sheets and across cell membranes is determinant for the pharmacokinetics of a drug.
Synthesis and Preclinical Evaluation of Sulfonamido based [11C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase
Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system.
Impact of curcumin on the pharmacokinetics of rosuvastatin in rats and dogs based on the conjugated metabolites
Plasma concentrations of curcumin-O-glucuronide (COG) and curcumin-O-sulfate (COS) significantly increased after Sprague-Dawley rats dealt with the Oatp inhibitor rifampicin, with the Cmax ascending 2.9...
Structure-based virtual screening, molecular docking, ADMET and molecular simulations to develop benzoxaborole analogs as potential inhibitor against Leishmania donovani trypanothione reductase
Visceral leishmaniasis (VL) is the most fatal form of leishmaniasis and it affects 70 countries worldwide. Increasing drug resistant for antileishmanial drugs such as miltefosine, sodium stibogluconate and...
Integration of Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Models with Adverse Outcome Pathways (AOPs) and Environmental Exposure Models to Screen for Environmental Hazards
A computational framework was developed to assist in screening and prioritizing chemicals based on their dosimetry, toxicity, and potential exposures.
Comparative human in-vivo study of an immediate release tablet over-encapsulated by gelatin and hydroxypropyl methyl cellulose capsules – impact of dissolution rate on bioequivalence
Rapid and consistent in-vivo drug dissolution is critical for drug absorption. In-vitro dissolutions tests are used to predict in-vivo disintegration and dissolution properties of drug products.