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Numerous methods are available for use as part of a virtual screening strategy but, as yet, no single method is able to guarantee both a level of confidence comparable to experimental screening and a level of computing efficiency that could drastically cut the costs of early phase drug discovery campaigns. Here, we present VSM-G (virtual screening manager(More)
In silico screening methodologies are widely recognized as efficient approaches in early steps of drug discovery. However, in the virtual high-throughput screening (VHTS) context, where hit compounds are searched among millions of candidates, three-dimensional comparison techniques and knowledge discovery from databases should offer a better efficiency to(More)
Virtual screening (VS) is becoming an increasingly important approach for identifying and selecting biologically active molecules against specific pharmaceutically relevant targets. Compared to conventional high throughput screening techniques, in silico screening is fast and inexpensive, and is increasing in popularity in early-stage drug discovery(More)
BACKGROUND The disposition of a pharmaceutical compound within an organism, i.e. its Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) properties and adverse effects, critically affects late stage failure of drug candidates and has led to the withdrawal of approved drugs. Computational methods are effective approaches to reduce the number of(More)
The human UDP-glucuronosyltransferase 1A6 (UGT1A6) plays important roles in elimination of many xenobiotics, including drugs. We have experimentally assessed inhibitory properties of 46 compounds toward UGT1A6 catalyzing the glucuronidation of 1-naphthol and built models for predicting compounds interactions with the enzyme. The tested compounds were(More)
β-Secretase (BACE) is a very promising target in the search for a treatment for Alzheimer's disease using a protein-ligand inhibition approach. Given the many published X-ray structures of BACE protein, structure-based drug design has been used extensively to support new inhibitor discovery programs. Due to the high flexibility and large catalytic site of(More)
Multidrug resistance associated protein 2 (MRP2/ABCC2) is a membrane transport protein that can potentially affect the disposition of many substrate drugs and their metabolites. Recently, we studied the interaction of a library of 432 compounds with ABCC2, and the structure-activity relationship (SAR) of a subset of 64 compounds divided into four scaffolds(More)
Volume of distribution and fraction unbound are two key parameters in pharmacokinetics. The fraction unbound describes the portion of free drug in plasma that may extravasate, while volume of distribution describes the tissue access and binding of a drug. Reliable in silico predictions of these pharmacokinetic parameters would benefit the early stages of(More)
Treatment of ocular disorders is a challenge due to the difficulty of delivering drugs to the target tissues within the eye at sufficient concentrations to produce a therapeutic effect. The cornea and the blood-retinal barrier, comprising of the retinal pigment epithelium and the retinal capillaries, are the main barriers for delivering drugs to treat(More)