Formulation changes are common during drug development either due to clinical or manufacturing considerations. These changes especially at later stages of drug development oftentimes raise questions...
Ligand-independent and tissue-selective androgen receptor inhibition by pyrvinium
Pyrvinium pamoate (PP) is a potent noncompetitive inhibitor of the androgen receptor (AR). Using a novel method of target identification, we demonstrate that AR is a...
Evaluation and Optimisation of Current Milrinone Prescribing for the Treatment and Prevention of Low Cardiac Output Syndrome in Paediatric Patients After Open Heart Surgery Using a Physiology-Based Pharmacokinetic Drug-Disease Model
Milrinone is the drug of choice for the treatment and prevention of low cardiac output syndrome (LCOS) in paediatric patients after open heart surgery across Europe.
Linking physiology to toxicity using DILIsym®, a mechanistic mathematical model of drug-induced liver injury
The drug development industry faces multiple challenges in the realization of safe effective drugs.
Small molecule kinase inhibitors approved by the FDA from 2000 to 2011: a systematic review of preclinical ADME data
Fourteen drugs targeting protein kinases have been approved by the United States Food and Drug Administration (FDA) between the years 2000 and 2011.
3D QSAR and pharmacophore study of curcuminoids and curcumin analogs: Interaction with thioredoxin reductase
Curcumin is the yellow pigment of Curcuma longa that irreversibly inhibits the activity of thioredoxin reductase (TrxR) and forms adduct.
Small-molecule inhibitors of the androgen receptor
The present invention provides tetrahydropyrvinium (THP), derivatives thereof, benzoxazole compounds, and derivatives thereof.
Preoperative androgen deprivation therapy for localized prostate cancer: delayed biochemical recurrence in high-risk disease
Background: The role of preoperative ADT for localized prostate cancer is controversial; prospective assessments have yielded varying results. We sought to define a subset...
A High-Throughput Screen against Pantothenate Synthetase (PanC) Identifies 3-Biphenyl-4-Cyanopyrrole-2-Carboxylic Acids as a New Class of Inhibitor with Activity against Mycobacterium tuberculosis
The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis. It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria...
Assessing the Risk of pH-Dependent Absorption for New Molecular Entities: A Novel in Vitro Dissolution Test, Physicochemical Analysis, and Risk Assessment Strategy
Weak base therapeutic agents can show reduced absorption or large pharmacokinetic variability when coadministered with pH-modifying agents, or in achlorhydria disease states, due to...
Purely in-silico BCS classification: Science based quality standards for the world’s drugs
BCS classification is a vital tool in the development of both generic and innovative drug products. The purpose of this work was to provisionally classify the world's top selling oral drugs...
Comparison of in silico models for prediction of mutagenicity
Using a dataset with more than 6000 compounds, the performance of eight quantitative structure activity relationships (QSAR) models was evaluated: ACD/Tox Suite, Absorption, Distribution...
A Simplified PBPK Modeling Approach for Prediction of Pharmacokinetics of Four Primarily Renally Excreted and CYP3A Metabolized Compounds During Pregnancy
During pregnancy, a drug's pharmacokinetics may be altered and hence anticipation of potential systemic exposure changes is highly desirable.
Incorporation of Physiologically Based Pharmacokinetic Modeling in the Evaluation of Solubility Requirements for the Salt Selection Process: A Case Study Using Phenytoin
In the pharmaceutical industry, salt is commonly used to improve the oral bioavailability of poorly soluble compounds. Currently, there is a limited understanding on the solubility...
Validation of quantitative structure–activity relationship models to predict water-solubility of organic compounds
Water-solubility is an important physicochemical property in pharmaceutical and environmental studies. We assessed the performance of five predictive computer models: ACD/PhysChem History...
Is the full potential of the Biopharmaceutics Classification System reached?
In this paper we analyse how the biopharmaceutics classification system (BCS) has been used to date. A survey of the literature resulted in a compilation of 242 compounds for which BCS classes were reported.
Bioisosteric approach in designing new monastrol derivatives: an investigation on their ADMET prediction using in silico derived parameters
Medicinal chemists are facing an increasing challenge to deliver safer and more effective medicines. An appropriate balance between drug-like properties such as solubility, permeability, metabolic stability...
Profiling Biopharmaceutical Deciding Properties of Absorption of Lansoprazole Enteric-Coated Tablets Using Gastrointestinal Simulation Technology
The aim of the present study was to correlate in vitro properties of drug formulation to its in vivo performance, and to elucidate the deciding properties of oral absorption.
Utility of Physiologically Based Modeling and Preclinical In Vitro/In Vivo Data to Mitigate Positive Food Effect in a BCS Class 2 Compound
Physiologically based pharmacokinetic (PBPK) modeling has become a useful tool to estimate the performance of orally administrated drugs.
Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery
Poor water-solubility is a common characteristic of drug candidates in pharmaceutical development pipelines today. Various processes have been developed to increase the solubility, dissolution rate...