A5065497953- Computational Drug Discovery Methods
- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Genetics, Bioinformatics, and Biomedical Research
- Malaria Research and Control
- Analytical Chemistry and Chromatography
- Microbial Natural Products and Biosynthesis
- Machine Learning in Materials Science
- Tuberculosis Research and Epidemiology
- Biomedical Text Mining and Ontologies
- Pharmacogenetics and Drug Metabolism
- Receptor Mechanisms and Signaling
- Synthesis and Catalytic Reactions
- Chemical Synthesis and Analysis
- vaccines and immunoinformatics approaches
- Cell Image Analysis Techniques
- Gene expression and cancer classification
- Trypanosoma species research and implications
- Scientific Computing and Data Management
- Phenothiazines and Benzothiazines Synthesis and Activities
- Cancer therapeutics and mechanisms
- Patient-Provider Communication in Healthcare
- Viral Infectious Diseases and Gene Expression in Insects
- Intellectual Property and Patents
- Biomedical Ethics and Regulation
Princess Alexandra Hospital
2022
European Bioinformatics Institute
2013-2018
Wellcome Trust
2013-2018
GlaxoSmithKline (United Kingdom)
2008-2018
Age UK
2018
South Western Sydney Local Health District
2017
Western Sydney University
2017
The University of Sydney
2016
Eli Lilly (United Kingdom)
2012
University of Sheffield
2007-2010
ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 and 2014 Nucleic Acids Research Database Issues. Since then, alongside continued extraction of data from medicinal chemistry literature, new sources have also been added to database. These include: deposited sets neglected disease screening; crop protection data; drug metabolism disposition patents. A number improvements features incorporated. include annotation assays targets...
ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 Nucleic Acids Research Database Issue. Since then, a variety of new data sources and improvements functionality have contributed to growth utility resource. In particular, more comprehensive tracking compounds from research stages through clinical development market provided inclusion United States Adopted Name applications; richer model for representing drug targets has been...
ChEMBL is now a well-established resource in the fields of drug discovery and medicinal chemistry research. The database curates stores standardized bioactivity, molecule, target data extracted from multiple sources, including primary literature. Programmatic access to has been improved by recent update web services (version 2.0.x, https://www.ebi.ac.uk/chembl/api/data/docs), which exposes significantly more underlying introduces new functionality. To complement data-focused services,...
Voltage-gated sodium channels drive the initial depolarization phase of cardiac action potential and therefore critically determine conduction excitation through heart. In patients, deletions or loss-of-function mutations channel gene, SCN5A , have been associated with a wide range arrhythmias including bradycardia (heart rate slowing), atrioventricular delay, ventricular fibrillation. The pathophysiological basis these clinical conditions is unresolved. Here we show that disruption mouse...
The increase of publicly available bioactivity data in recent years has fueled and catalyzed research chemogenomics, mining, modeling approaches. As a direct result, over the past few multitude different methods have been reported evaluated, such as target fishing, nearest neighbor similarity-based methods, Quantitative Structure Activity Relationship (QSAR)-based protocols. However, studies are typically conducted on datasets, using validation strategies, metrics. In this study, were...
SureChEMBL is a publicly available large-scale resource containing compounds extracted from the full text, images and attachments of patent documents. The data are literature according to an automated text image-mining pipeline on daily basis. provides access previously unavailable, open timely set annotated compound-patent associations, complemented with sophisticated combined structure keyword-based search capabilities against compound repository document corpus; given wealth knowledge...
The emergence of a number publicly available bioactivity databases, such as ChEMBL, PubChem BioAssay and BindingDB, has raised awareness about the topics data curation, quality integrity. Here we provide an overview discussion current future approaches to activity, assay target curation ChEMBL database. This process involves several manual automated steps aims to: (1) maximise accessibility comparability; (2) improve integrity flag outliers, ambiguities potential errors; (3) add further...
Previous studies of the analysis molecular matched pairs (MMPs) have often assumed that effect a substructural transformation on property is independent context (i.e., local structural environment in which occurs). Experiments with large sets hERG, solubility, and lipophilicity data demonstrate inclusion contextual information can enhance predictive power MMP analyses, significant trends (both positive negative) being identified are not apparent when using conventional, context-independent...
The development of new antimalarial compounds remains a pivotal part the strategy for malaria elimination. Recent large-scale phenotypic screens have provided wealth potential starting points hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared real time, anyone was able to participate, patents not sought. chemical subseries found exhibit oral activity but contained labile ester that could be replaced...
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects an estimated two billion people worldwide and is leading cause mortality due to infectious disease. The development new anti-TB therapeutics required, because emergence multi-drug resistance strains as well co-infection with other pathogens, especially HIV. Recently, pharmaceutical company GlaxoSmithKline published results a high-throughput screen (HTS) their million compound library for anti-mycobacterial...
In view of the need to continuously feed pipeline with new anti-malarial agents adapted differentiated and more stringent target product profiles (e.g., modes action, transmission-blocking activity or long-duration chemo-protection), a chemical library consisting than 250,000 compounds has been evaluated in blood-stage Plasmodium falciparum growth inhibition assay further assessed for diversity novelty. The selection cascade used triaging hits from started robust three-step vitro followed by...
Drug discovery programs frequently target members of the human kinome and try to identify small molecule protein kinase inhibitors, primarily for cancer treatment, additional indications being increasingly investigated. One challenges is controlling inhibitors degree selectivity, assessed by in vitro profiling against panels kinases. We manually extracted, compiled, standardized such profiles published literature: we collected 356 908 data points corresponding 482 kinases, 2106 661 patents....
The lack of success in target-based screening approaches to the discovery antibacterial agents has led reemergence phenotypic as a successful approach identifying bioactive, compounds. A challenge though with this route is then identify molecular target(s) and mechanism action hits. This target identification, or deorphanization step, often essential further optimization validation studies. Direct experimental identification hit complex, precisely because properties specificity are not yet...
As a follow up to the antimycobacterial screening exercise and release of GSK´s first Tres Cantos Antimycobacterial Set (TCAMS-TB), this paper presents results second antitubercular effort two hundred fifty thousand compounds recently added GSK collection. The were further prioritized based on not only potency but also physicochemical characteristics. 50 most attractive then progressed for evaluation in three different predictive computational biology algorithms structural similarity or...
Abstract Bioisosterism is a key concept in medicinal chemistry, as it allows chemists to interchange structural fragments without significant perturbation biological activity. Not surprisingly, given the vast amount of bioactivity data and chemoinformatics resources now available, there has been surge number computational approaches available mine identify bioisosteric replacements for bioactive compounds. Such methods have certainly provided with diverse arsenal in‐house, commercial,...
First public disclosure of new chemical entities often takes place in patents, which makes them an important source information. However, with ever increasing number patent applications, manual processing and curation on such a large scale becomes even more challenging. An alternative approach better suited for this corpus documents is the automated extraction structures. A chemistry databases generated by using latter are now available but little known that can help to manage expectations...
Mycobacterium phenotypic hits are a good reservoir for new chemotypes the treatment of tuberculosis. However, absence defined molecular targets and modes action could lead to failure in drug development. Therefore, combination ligand-based structure-based chemogenomic approaches followed by biophysical biochemical validation have been used identify tuberculosis hits. Our approach identified EthR InhA as several hits, with some showing dual activity against these proteins. From 35 predicted...
UniChem is a low-maintenance, fast and freely available compound identifier mapping service, recently made on the Internet. Until now, criterion of molecular equivalence within has been basis complete identity between Standard InChIs. However, limitation this approach that stereoisomers, isotopes salts otherwise identical molecules are not considered as related. Here, we describe how have exploited layered structural representation InChI to create new functionality integrates these related...
The development of new antimalarial therapies is essential, and lowering the barrier entry for screening discovery lead compound classes can spur drug at organizations that may not have large libraries or resources to conduct high-throughput screens. Machine learning models been long established be more robust a larger domain applicability with training sets. Screens over multiple data sets find compounds potential malaria blood stage inhibitory activity used generate Bayesian models. Here...
ChEMBL is a large-scale drug discovery database containing bioactivity information primarily extracted from scientific literature. Due to the medicinal chemistry focus of journals which data are extracted, currently most direct value in field human health research. However, many use-cases for current set equally applicable other fields, such as crop protection research: example, identification chemical scaffolds active against particular target or endpoint, de-convolution potential targets...