The ChEMBL-og

Last year, MMV released the MMV Malaria Box , a physical set of 400 probe- and drug-like compounds with confirmed anti-malarial activity. The 'Box' has been since distributed to a large number of academic labs around the world, where the compounds are screened against other plasmodia strains and pathogens such as schistosoma and mTB. The assay results have started coming back in the form of data depositions and, we, as MMV partners, are doing our best to integrate them with both the malaria-data database, as well as the main ChEMBL one. Recent examples of such MMV Malaria Box screening data depositions include: An mTB screen by the Nathan lab in Cornell A schistosoma screen by  Conor Caffrey  and colleagues in UCSF A  plasmodium apicoplast screen by the Derisi lab in UCSF, as reported in our post last week In addition, we curate and integrate the bioactivity data produced by the excellent  Open Source Malaria project. The value of shari...

We have just had a paper published in Bioinformatics on myChEMBL - the Linux VM that contains a fully functional version of the ChEMBL database. The paper is here . myChEMBL is available for download at: ftp://ftp.ebi.ac.uk/pub/databases/chembl/VM/myChEMBL/current A warning, it is a fairly big download ( ca. 18GB, so try and do this over a fast stable connection) Source code is available here: https://github.com/rochoa85/myChEMBL %T myChEMBL: A virtual machine implementation of open data andcheminformatics tools %J Bioinformatics %D 2013 %O DOI:10.1093/bioinformatics/btt666 %A M. Davies %A G. Papadatos %A F. Atkinson %A J.P. Overington

Some of our collaborators at the Karolinska have a great job available - the advert is here . Division Chemical Biology Consortium Sweden (CBCS) are looking for a highly motivated and talented Cheminformatics Scientist to support and coordinate a wide scope of research informatics applications and data analysis at our Stockholm facilities. Duties The desired candidate will have a demonstrated track record in managing large volumes of scientific data in support of basic research and/or drug discovery projects and should have significant experience with in-house and commercial software solutions that facilitate data capture, analysis and visualization in small molecule research and drug design. Responsibilities include: Evaluation and implementation of a nationally encompassing chemoinformatics system for the SciLifeLab community. Maintainance, configuration, monitoring, and/or troubleshooting scientific applications and underlying software.  Partnering and interaction ...

Teach-Discover-Treat (TDT) is excited to announce our 2014 Competition. We have four exciting challenges that focus on developing and disseminating computational workflows for drug discovery of neglected diseases with a premium on reproducibility. Three cash prizes - plus partial reimbursement of travel - will be awarded! Winners are required to present their work at the TDT Award symposium during the Fall 2014 ACS National Meeting in San Francisco, California. Create and submit computational workflows that inspire drug discovery activities using freely available software tools. Detailed informationabout the 2014 Competition can be found here:  http://www.TDTproject.org/ 2014-competition.html Submissions deadline is  February 3, 2014 . The TDT Steering Committee Hanneke Jansen, Rommie Amaro, Jane Tseng, Wendy Cornell, Patrick Walters and Emilio Xavier Esposito @TeachDiscoTreat

ATC Code: Wikipedia: Ibrutinib On November 13, 2013, the FDA approved Ibrutinib (Imbruvica TM ) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. MCL is a subtype of B-cell lymphoma and accounts for 6% of non-Hodgkin's lymphoma cases. In an open-label, multi-center, single-arm trial of 111 previously treated patients, Ibrutinib showed a 65.8% response rate. Ibrutinib is an irreversible inhibitor of the Tyrosine-protein kinase BTK (Uniprot:Q06187; ChEMBL: CHEMBL5251 ; canSAR target synopsis ) and is the first approved targeted BTK inhibitor. It forms a covalent bond with a cysteine residue via a Michael acceptor mechanism, in the BTK active site, leading to inhibition of BTK enzymatic activity Ibrutinib (ChEMBL: CHEMBL1873475 ; canSAR drug synopsis ; also known as CRA-032765 and PCI-32765) has the formula C25H24N6O2 and a molecular weight 440.50. It is absorbed after oral administration with a median Tma...

ATC Code:  L01XC15 Wikipedia: Obinutuzumab On November 1, 2013 the FDA approved obinutuzumab (Gazyva TM ) for use in combination with chlorambucil  (a nitrogen mustard alkylating agent) for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). CLL is the most common type of Leukaemia accounting for 35% of all reported Leukaemias (See CRUK CLL page). In a randomized three-arm clinical study, the combination of obinutuzumab (in combination with chlorambucil) improved the progression-free survival (PFS) of patients to 23.0 months compared to 11.1 months for chlorambucil alone. Obinutuzumab ( CHEMBL1743048 ) is a humanized anti-CD20 monoclonal antibody of ca . 150 kDa molecular weight. Its target, the B-lymphicyte antigen CD20, is the product of the gene MS4A1 (Uniprot: P11836; ChEMBL: CHEMBL2058 ; canSAR target synopsis . The CD20 antigen is expressed on the surface of pre B- and mature B-lymphocytes. Obinutuzumab mediates B-ce...

We are very pleased to announce the release of two new datasets on the ChEMBL-NTD portal. The first dataset is provided by the Drug for Neglected Diseases initiative (DNDi) and is focused on the selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi . The paper describing the dataset in more detail can be accessed here and the data can be downloaded from here .   The second dataset from the DeRisi Lab UCSF and is focused on the screening of MMVs Malaria Box compounds in Plasmodium falciparum , to understand if anti-malarial compounds target the apicoplast organelle. More details about the dataset can be found here and the data can be downloaded from here .   Both datasets will be loaded into the next version of ChEMBL, which will be due out early next year. The ChEMBL - Neglected Tropical Disease portal is a repository for Open Access primary screening and medicinal chemistry data directed at neglected diseases. ...

The ChEMBL group had the honour of hosting the second RDKit UGM . It was a great way to catch up with the RDKit community, find out about what they are working and learn about new features the toolkit offers. We gave two talks during the meeting, so if you want to know how Clippy can make interacting with different chemical formats on your desktop easier, go here , and if you want to learn about wrapping RDKit up in a RESTful Web Service a.k.a. Beaker (to be described in future blog post), go here . Many discussions about new features RDKit could offer were had throughout the meeting and one which caught my attention was support for plotting compound images on HTML5 Canvas . Unable to participate in a hackathon held on the final day, I set about hosting my own small hackathon during the weekend (only 1 attendee). The result of this weekend coding effect was a pull request made against RDKit github repo , introducing the new class called JSONCanvas . Technical Details As a ge...

The USANs for September, 2013 have recently been published. We actually missed September, due to switch over in service for the INNs, but now they're here. USAN Research Code InChIKey (Parent) Drug Class Therapeutic class Target aducanumab BIIB-037 n/a monoclonal antibody therapeutic beta amyloid aptorsen-sodium OGX-427 n/a oligonucleotide therapeutic HSP27 asfotase-alfa ALXN-1215, ENB-0040 n/a enzyme therapeutic n/a batefenterol ,  batefenterol-succinate GSK-961081A URWYQGVSPQJGGB-DHUJRADRSA-N synthetic small molecule therapeutic Muscarinic ...

An update to what has happen to the Wellcome Trust funded database  ChEMBL  over the past few years has just been published - it seems odd, that we've been around long enough to achieve our 2nd NAR Database paper - so much more to do though! This paper contains features and content up to ChEMBL 17. This could put you in a difficult position which NAR paper to cite in your own publications using ChEMBL; so we suggest both! ;) Oh, and it's Open Access, of course. %J Nucleic Acids Research %D 2013 %P 1–8 %O doi:10.1093/nar/gkt1031 %T The ChEMBL bioactivity database: an update %A A.P. Bento %A A. Gaulton %A Anne Hersey %A L.J. Bellis, %A J. Chambers %A M. Davies %A F.A. Krueger %A Y. Light %A L. Mak %A S. McGlinchey %A M. Nowotka %A G. Papadatos %A R. Santos %A J.P. Overington jpo

Here 's an Open Access paper from Samuel in the group. Drug repositioning is the discovery of new indications for compounds that have already been approved and used in a clinical setting. Recently, some computational approaches have been suggested to unveil new opportunities in a systematic fashion, by taking into consideration gene expression signatures or chemical features for instance. We present here a novel method based on knowledge integration using semantic technologies, to capture the functional role of approved chemical compounds. In order to computationally generate repositioning hypotheses, we used the Web Ontology Language (OWL) to formally define the semantics of over 20,000 terms with axioms to correctly denote various modes of action (MoA). Based on an integration of public data, we have automatically assigned over a thousand of approved drugs into these MoA categories. The resulting new research resource is called the Functional Therapeutic Chemical C...

A few days ago, there was this post by Derek Lowe, reviewing a recent paper on magic methyls and their occurrence and impact in medicinal chemistry practice. They're called 'magic' because, although methyls are relatively insignificant in terms of size, polarity or lipophilicity, the addition of one in a compound can  sometimes  have a dramatic impact in its potency - much more that it would be attributed to any simple desolvation effects. More generally, the 'magic methyl' phenomenon pops up in discussions about the validity of the  molecular similarity  principle, descriptors, QSAR - almost everything in the applied Chemoinformatics field - and belongs to the general class of ' activity cliffs '.  Methylation is a chemical transformation, and transformations along with their impact on a property of choice can be easily mined and studied using the so-called Matched Molecular Pairs analysis ( MMPA ). We already have a comprehensive da...

ATC Code: V09AX04 On October 25 th , the FDA approved Flutemetamol F18 (Tradename: Vizamyl ; Research Code: [ 18 F]AH110690 ), a radioactive diagnostic agent, for intravenous (i.v.) use in Positron Emission Tomography (PET) imaging of the brain in adult patients with cognitive impairment , who are being evaluated for Alzheimer’s disease (AD) and dementia. Alzheimer's disease is a non-treatable, progressively worsening and fatal disease, characterised by a decrease in cognitive functions, such as memory, and is usually associated with an accumulation of β amyloid (Uniprot: P05067 ) plaques in several brain regions. These deposits are believed to be responsible for cellular damage and ultimately cell death. Flutemetamol F18 is the second approved diagnostic drug to estimate β-amyloid neuritic plaque density, after the approval of Florbetapir F18 in 2012. Like Florbetapir F18, Flutemetamol F18 binds to β amyloid plaques in the brain where the F-18 isotope produces...