Showing papers in "Drug Discovery Today: Technologies in 2015"

TL;DR: The use of NMR- or MS-based metabolomics is proposed as an efficient approach to find antimicrobials in microbial single- or co-cultures.

TL;DR: This article reviews various approaches to monitor SKR and suggests using the on-rate as the key monitoring parameter and examples of compound series with low variability as well as with significant changes in on-rates are highlighted.

TL;DR: Kinase profiling work seeks to understand general selectivity trends of lead compounds across the kinome, which help with target selection, compound prioritization, and potential implications in toxicity.

TL;DR: The International Chemical Identifier (InChI) as discussed by the authors is a non-proprietary line-notation for describing a chemical structure that can be used to identify compounds that are the same at various levels of similarity, such as those containing the same parent component or having the same connectivity.

TL;DR: The challenge in metabolomics is to find a technological approach allowing the reproducible identification and quantitation of as much metabolites as possible, and mass spectrometry and NMR are emerging as key and complementary technologies.

TL;DR: In this article, the authors describe typical lipidomics set-ups and illustrate how these technologies can be implemented in target discovery, compound screening, in vitro and in vivo preclinical testing, toxicity testing of drugs, and prediction and monitoring of response.

TL;DR: This review outlines key modeling techniques in both systems biology models and pharmacological models and to subsequently discuss challenges and opportunities for further integration, in oncology drug development.

TL;DR: This review highlights why NMR could be considered a key tool for the application of metabolomics in drug discovery.

TL;DR: This paper reviews NMR methods for speciation of precious metal anti-cancer complexes, including platinum-group and gold-based anti- cancer agents, and examples of NMR studies involving interactions with DNA and proteins are highlighted.

TL;DR: It is reviewed here how experimental and computational network-based approaches can aid more rational drug target selection and illustrate this with results obtained for microbes and for cancer.

TL;DR: In the era of big data medicinal chemists are exposed to an enormous amount of bioactivity data, but the data available are still quite incomplete and of mixed quality.

TL;DR: The establishment of 'virtual patient' models centred on a detailed molecular characterisation of thousands or even, in the future, millions of patients lays the foundations for truly personalised therapy, as well as a far-reaching virtualisation of drug discovery and development in oncology and other areas of medicine.

TL;DR: The general principles and applications of several methods based on affinity chromatography, including band-broadening measurements, peak decay method, peak fitting methods, the split-peak method, and free fraction analysis are examined.

TL;DR: In this paper, the authors discuss areas where metabolomic technologies and applications are poised to have the greatest impact in the discovery and development of pharmaceuticals, focusing on applications in toxicology and disease pathology, more recent academic and commercial efforts have helped advance metabolomics as a tool to reveal the molecular basis of biological processes and pharmacological responses to drugs.

TL;DR: Findings of the network nature of disease suggest ways in which pharmacokinetics, pharmacodynamics, but also systems biology and genomics may have to change so as better to deal with systems-biology diseases.

TL;DR: A generalized approach is proposed that combines high quality kinetic and equilibrium data in an Integrated Global Fit analysis yielding the most probable binding mechanism.

TL;DR: The Big-Bang of open automated extraction since 2012 has contributed to over 15 million patent-derived compounds in PubChem as discussed by the authors, and these relationships can be harvested using open tools and are beginning to be curated into databases.

TL;DR: Epigenetic factors, which confer, remove or recognize covalent modifications to chromatin DNA or proteins, can be divided into three broad groups, commonly referred to as the 'writers', 'erasers' and 'readers'.

TL;DR: In this article, intact cells were used for radioligand binding assays on intact cells, which can provide insights into induced-fit type binding, receptor internalization and even into pharmacomicrokinetic phenomena like drug rebinding and partitioning into the membrane.

TL;DR: The reports of the application of mechanistic systems models to drug discovery questions are reviewed and the added value of these approaches is discussed.

TL;DR: As inhibitors with new chemical scaffolds are of particular interest to improve HDAC isoform-specificity and pharmaceutical properties, effective profiling technologies will continue to have important utility.

TL;DR: Current cellular methodologies for HMT and HDM drug discovery support are highlighted and it is anticipated that implementation of these cell-based assays will positively impact the discovery of pharmacologically potent HMT or HDM inhibitors.

TL;DR: Capillary electrophoresis is a separation method based on differential migration of analytes in electric fields that has high potential to facilitate the development of metallodrugs, especially when combined with innovative method development and experimental design.

TL;DR: Systems toxicology as applied to the effects of paracetamol (acetaminophen, N-acetyl-para-aminophenol (APAP)) is used to exemplify the potential of the approach and to facilitate the discovery of safe new drugs.

TL;DR: How metabonomics, one of the key players in systems biology, should be able to assist toxicologists in better predicting the adverse effects of xenobiotics is reviewed.

TL;DR: How kinase profiling was used in early stage drug discovery efforts, from the perspective of a smaller biotech relying largely on assay outsourcing is discussed.

TL;DR: Three main areas of GPCR profiling are discussed including pharmacologically relevant hit identification, the pharmacology dossier applied to parallel structure activity and structure liability relationships and high-throughput mechanism studies from genotype to phenotype.

TL;DR: This review aims to provide an overview of ion channel profiling for cardiac safety and comparisons of various technologies.

TL;DR: The results suggest that the developed LC-method is useful to probe the fate of biologically active novel metal-complexes in plasma to help select those which may be advanced to animal/clinical studies to ultimately develop safer metallodrugs.