The emergence of metabolomics as a key discipline in the drug discovery process
Publication date: Available online 28 February 2015 Source:Drug Discovery Today: Technologies Author(s): Marianne Fillet , Michel Frédérich Metabolomics is a recent science that could be defined as the comprehensive qualitative and quantitative analysis of all small molecular weight compounds present in a cell, organ (including biofluids) or organism at a specific time point. More and more applications have been found these past years to metabolomics in the pharmaceutical field. Specifically in the drug discovery process, metabolomics open new perspectives, in new targets identification, in toxicological studies an...
Source: Drug Discovery Today: Technologies - March 2, 2015 Category: Drugs & Pharmacology Source Type: research
Expanding opportunities for mining bioactive chemistry from patents
Publication date: Available online 10 February 2015 Source:Drug Discovery Today: Technologies Author(s): Christopher Southan Bioactive structures published in medicinal chemistry patents typically exceed those in papers by at least twofold and may precede them by several years. The Big-Bang of open automated extraction since 2012 has contributed to over 15 million patent-derived compounds in PubChem. While mapping between chemical structures, assay results and protein targets from patent documents is challenging, these relationships can be harvested using open tools and are beginning to be curated into databases. Gra...
Source: Drug Discovery Today: Technologies - February 13, 2015 Category: Drugs & Pharmacology Source Type: research
Surface Plasmon Resonance biosensor analysis as a useful tool in FBDD
Publication date: Autumn 2010 Source:Drug Discovery Today: Technologies, Volume 7, Issue 3 Author(s): Kim Retra , Hubertus Irth , Jacqueline E. van Muijlwijk-Koezen SPR (Surface Plasmon Resonance) biosensor instruments are more and more equipped to sensitively measure the binding characteristics of small molecules to their target. Via SPR biosensor measurements, not only the affinity of compounds but also other features such as the kinetics and thermodynamics aspects of binding can be determined. Furthermore, SPR is able to determine nonideal behavior of the fragment, such as aggregation and poor solubility binding....
Source: Drug Discovery Today: Technologies - December 11, 2014 Category: Drugs & Pharmacology Source Type: research
Ligand efficiency as a guide in fragment hit selection and optimization
Publication date: Autumn 2010 Source:Drug Discovery Today: Technologies, Volume 7, Issue 3 Author(s): Sabine Schultes , Chris de Graaf , Eric E.J. Haaksma , Iwan J.P. de Esch , Rob Leurs , Oliver Krämer Fragment-based screening (FBS) has become an established approach for hit identification. Starting points identified by FBS, are small fragments that require substantial modification to become leads. As fragments are different from classical hits a process tailored for fragment evolution is required. Scores for ligand efficiency have been proposed as guides for this process. Here we review how these have been app...
Source: Drug Discovery Today: Technologies - December 11, 2014 Category: Drugs & Pharmacology Source Type: research
Humanised models of infection in the evaluation of anti-malarial drugs
Publication date: September 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 3 Author(s): Iñigo Angulo-Barturen , Santiago Ferrer Humanised mice have a crucial role for drug discovery in malaria, which is the most important parasitic disease in the world and is caused by protozoa of the genus Plasmodium that selectively infect human hepatocytes and erythrocytes. There are currently reliable humanised murine models for hepatic and erythrocytic stages of Plasmodium falciparum, which is the most pathogenic malarial species. These models are useful in the evaluation of drugs for malaria prevention and tr...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Technologies: preclinical imaging for drug development
Publication date: September 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 3 Author(s): Paul M. Matthews , Robert Coatney , Hasan Alsaid , Beat Jucker , Sharon Ashworth , Christine Parker , Kumar Changani Preclinical imaging with magnetic resonance imaging (MRI), computerised tomography (CT), ultrasound (US), positron emission tomography (PET) or single-photon emission computed tomography (SPECT) enable non-invasive measures of tissue structure, function or metabolism in vivo. The technologies can add value to preclinical studies by enabling dynamic pharmacological observations on the same anim...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Evaluation of symptomatic drug effects in Alzheimer's disease: strategies for prediction of efficacy in humans
Publication date: September 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 3 Author(s): J. Deguil , L. Ravasi , A. Auffret , C. Babiloni , D. Bartres Faz , V. Bragulat , C. Cassé-Perrot , V. Colavito , M.T. Herrero Ezquerro , Y. Lamberty , L. Lanteaume , D. Pemberton , F. Pifferi , J.C. Richardson , E. Schenker , O. Blin , E. tarragon , R. Bordet In chronic diseases such as Alzheimer's disease (AD), the arsenal of biomarkers available to determine the effectiveness of symptomatic treatment is very limited. Interpretation of the results provided in literature is cumbersome and it bec...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Animal models of Alzheimer's disease and drug development
Publication date: September 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 3 Author(s): Bart Laurijssens , Fabienne Aujard , Anisur Rahman Animal disease models are considered important in the development of drugs for Alzheimer's disease. This brief review will discuss possible reasons why their success in identifying efficacious treatments has been limited, and will provide some thoughts on the role of animal experimentation in drug development. Specifically, none of the current models of Alzheimer's disease have either construct or predictive validity, and no model probably ever will. Clearly, sp...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Translational pharmacology: from animal to man and back
Publication date: September 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 3 Author(s): Oscar Della Pasqua (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Small molecules modulation of 14-3-3 protein–protein interactions
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Mattia Mori , Giulia Vignaroli , Maurizio Botta 14-3-3 is a family of highly conserved regulatory proteins which is attracting a significant interest due to its potential role as target for pharmacological intervention against cancer and neurodegenerative disorders. Although modulating protein–protein interactions (PPI) is still conceived as a challenging task in drug discovery, in past few years peptide inhibitors and small molecular modulators of 14-3-3 PPI have been described. Here we examine structural and ...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Inhibition of PDZ domain-mediated interactions
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Dolors Grillo-Bosch , Daniel Choquet , Matthieu Sainlos Modulating protein–protein interactions constitutes a promising strategy both for the investigation of biological mechanisms and for developing new therapeutic approaches. Among the many types of interactions, PDZ domain-mediated interactions (PDMIs) have emerged over the last decade as attractive targets in the drug discovery field. Indeed, these small domains are involved in the regulation of many signaling pathways and possess structural properties whic...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Small molecule inhibitors of the HIV-1 virulence factor, Nef
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Thomas E. Smithgall , Gary Thomas Although antiretroviral therapy has revolutionized the clinical management of AIDS, life-long treatment is required because these drugs do not eradicate HIV-infected cells. Chronic antiretroviral therapy may not protect AIDS patients from cognitive impairment, raising important quality of life issues. Because of the rise of HIV strains resistant to current drugs and uncertain vaccine prospects, an urgent need exists for the discovery and development of new therapeutic approaches. ...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Rational design of LEDGINs as first allosteric integrase inhibitors for the treatment of HIV infection
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Belete A. Desimmie , Jonas Demeulemeester , Frauke Christ , Zeger Debyser The interaction between lens epithelium-derived growth factor (LEDGF/p75) and HIV-1 integrase (IN) is an attractive target for antiviral development because its inhibition blocks HIV replication. Developing novel small molecules that disrupt the LEDGF/p75–IN interaction constitutes a promising new therapeutic strategy for the treatment of HIV. Here we will highlight recent advances in the design and development of small-molecule inhibito...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Inhibitors of protein–protein interactions: New methodologies to tackle this challenge
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Laura Silvian , Istvan Enyedy , Gnanasambandam Kumaravel Several advances in the fields of crystallography, molecular modeling, biophysical assays and chemistry are converging to making protein–protein interaction targets more amenable to drug design. These include steps towards improving crystallization of protein–protein complexes, identifying the clusters of residues that constitute putative small molecule binding ‘hot spots’, generating new methods for detecting the binding of small molecules to targe...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
Probing structural adaptivity at PPI interfaces with small molecules
Publication date: December 2013 Source:Drug Discovery Today: Technologies, Volume 10, Issue 4 Author(s): Christopher G. Wilson , Michelle R. Arkin There is strong interest in developing small molecules that modulate protein-protein interactions (PPI), since such compounds could serve as drug leads or as probes of protein function. Fragment-based ligand discovery has been a particularly useful approach for modulating PPI. Fragments are typically <250Da compounds that bind to proteins with weak affinity but high ligand efficiency. Here, we review a method for fragment-based ligand discovery using covalent disulf...
Source: Drug Discovery Today: Technologies - October 12, 2014 Category: Drugs & Pharmacology Source Type: research
