The ChEMBL-og

As promised before , there will be a webinar on accessing  ChEMBL REST web services via KNIME and Pipeline Pilot  at 3.30 pm BST on Wednesday, 8th August 2012 . Please  email  me in advance in order to register for this.

ATC Code: R03BB05 Wikipedia: Aclidinium bromide On July 23 th , the FDA approved Aclidinum bromide (Tradename: Tudorza   Pressair TM ; Research Codes: LAS-34273, LAS W-330), a muscarinic acetylcholine M 3 receptor antagonist, for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD) . Chronic obstructive pulmonary disease (COPD) is characterised by the occurrence of chronic bronchitis or emphysema , a pair of commonly co-existing diseases of the lungs in which the airways become narrowed. Bronchial spasms, a sudden constriction of the muscles in the walls of the bronchioles , occur frequently in COPD. Aclidinum bromide is a long-acting antimuscarinic agent that through the inhibition of the muscarinic acetylcholine M 3 receptors present in the airway smooth muscle, leads to bronchodilation, and consequently eases the symptoms of COPD. The muscarinic acetylcholine M 3 receptor (Uniprot: P203...

There's now a BioRuby  API for ChEMBL, written by the excellent Mitsuteru Nakao ( @32nm on twitter). Bio-chembl is a bioruby plugin built on top of the ChEMBL REST web services  -  https://github.com/nakao/bio-chembl Of course, there is also the pychembl project in Python from Marcus Sitzmann of the NCI. -  https://github.com/markussitzmann/pychembl And I've just been reminded of the R ChEMBL package from Rajarshi Guha  -  https://github.com/rajarshi/chemblr   However, the real mark of success will be when we get a ChEMBL f77 library!

ATC Code: L01XX Wikipedia: Carfilzomib On July 20th 2012 the FDA approved Carfilzomib (Kyorolis TM ) for the treatment of patients with multiple myeloma who have received prior therapies including bortezomib and an immunomodulatory therapy, and who have demonstrated disease progression within 60 days of completion of the previous therapy. Multiple myeloma is a cancer of the Plasma Cells and usually in the bone marrow. Five year survival is about 40% in the UK and and the USA . Carfilzomib is a chirally defined modified tetrapeptidyl epoxide substrate analogue with a molecular weight of 719.9. The molecular formula is C40H57N5O7. (SMILES= O=C(N[C@H](C(=O)N[C@H](C(=O)N[C@H(C(=O)N[C@H](C(=O)[C@@]1(OC1)C)CC(C)C)Cc2ccccc2)CC(C)C)CCc3ccccc3)CN4CCOCC4) Cmax and AUC following a single intravenous dose of 27 mg/m2 was 4,232 ng/mL and 379 ng.hr/mL, respectively. The mean steady-state volume of distribution of a 20 mg/m2 dose of carfilzomib was 28 L. Carfilzomib was rapidly an...

When a screen and follow-up have failed to deliver an attractive lead for a 'hard' target, talk amongst the team often turns to running a screen for an allosteric inhibitor; Allosteric regulators are therefore a seductive/tantalising approach to find leads against tough targets such as protein-protein interactions, highly polar binding sites, etc . But, there's a few hard questions to answer, this is just a few. Just how do I run a screen for an allosteric inhibitor? What compounds do I select for allosteric sites? How likely am I to find an allosteric inhibitor?  What sorts of targets can be allosterically modulated? What are the 3-D properties of allosteric sites I've read some of the literature behind the arguments for allosteric inhibitors, and I must say I'm not that convinced as to their general potential benefits at the moment - of course in some cases, they will be perfect, but are the advantages as general as people may think. But I've been...

We are pleased to announce the release of ChEMBL_14. This latest version of the ChEMBL database contains: 1,384,479 compound records 1,213,242 distinct compounds 644,734 assays 10,129,256 bioactivities 9,003 targets 46,133 documents 10 data sources As well as updates to the scientific literature and PubChem data sources, this release also includes data from 2 new sources: DrugMatrix - in vitro pharmacology assays for 870 therapeutic, industrial and environmental chemicals against 132 protein targets.  GSK Published Kinase Inhibitor Set - two data sets screening this compound library have been deposited by Nanosyn and the University of North Carolina. On the interface, we have also added some new compound cross references to Gene Expression Atlas , Drugs of the Future (subset of PubChem) , IUPHAR , NIH Clinical Collection and ZINC . On the target report card pages we have added cross references to CanSAR , Gene Ontology , IntAct , InterPro , IUPHAR , MICAD , R...

As announced also  here , a new malaria data service is available today to researchers around the globe sponsored by the Medicines for Malaria Venture ( MMV ). The service provides access to hundreds of thousands of data points on malaria-related compounds, assays and targets, thus facilitating research for this neglected tropical disease. Inspired by the successful ChEMBL interface, a user may query the database using keywords, synonyms, chemical structures or protein sequences, review and filter the hits using tables or charts and then download the resulting subset. Data provenance is also provided so that the user can filter on the data sources they are interested in, such as scientific literature, the GlaxoSmithKline TCAMS, Novartis GNF and St Jude datasets or the MMV open access Malaria Box . Based on the ChEMBL update cycle, the malaria data database will be regularly updated with depositions by academic and industrial groups who wish to share their malaria screen...

There was a post a few weeks ago about elemental compositions - simple cases of Carbon oxides, nitrogen oxides, etc . Well, I've processed ChEMBL to do the analysis across all of the compounds - very simple analysis - select all formulas of all compounds, select only those that are contain only elements restricted to the set CHNO, and then plot the heavy element ( i.e. C N or O) fractions on a ternary plot . Here it is (click image for larger). So, the compounds that chemists make are mostly carbon-based, and of course, there's no contours on this version of the plot - hardly a big surprise, that's why they are organic, but things get more interesting when you think about using these data as filters/heuristics for expectation values for the sort of things that chemists could make, for spotting unusual compounds, etc . etc . More later on this... Update: Here is the plot for drugs. As you will see there are some differences...

There's a great paper just out from some of our collaborators - Bissan Al-Lazikani, Udai Banerji and Paul Workman, of the ICR. It reviews drug combination strategies for cancer, and some of the molecular features of effective drug combinations. A link to the paper is here . %A B. Al-Lazikani %A U. Banerji %A P. Workman %T Cobminatorial Drug Therapy For Cancer in the Post-genomic Era %J Nat. Biotech. %V 30 %P 1-13 %D 2012 %O DOI:

This new blog post has been created due to popular demand and user requests. I hope that this is useful for you. After being manually extracted from the primary literature, a compound can be only loaded into the ChEMBL database after it has been run through our in-house clean-up protocol. This protocol utilises Accelrys 's Pipeline Pilot software and has evolved a lot over the past three years. The clean-up protocol is used to prevent any structures from being loaded that could be incorrect, not properly charged or contain bad valences. We also use it to map the structures to already existing compounds in ChEMBL. Historically, the clean-up protocol was very simple with just a few components to squeeze out any unwanted structures. Initially, we were mostly concerned about having uneven charges (e.g. charged counter ion but neutral parent) or quaternary nitrogen-containing compounds without a counter ion at all. Over the past 14 releases, the clean-up has become more sophisti...

A great looking conference on toxicity prediction to be held at Downing College, Cambridge on September 5th and 6th 2012 - a fantastic line up of speakers, and organised by one of our favourite collaborators LHASA Limited . Details of the conference, registration, etc . are here .

So, the course is over for another year. It was really good fun to do, and thanks to all the attendees who made it really rewarding for us all. There is plenty for us to think about in what you asked, and we'll try and include a few more things in the ChEMBL interface. An especial thanks goes out to our visiting lecturers - John Irwin, Noel O'Boyle, Markus Sitzmann, Val Gillet, Andreas Bender, Darren Green, Bissan Al-Lazikani and Mike Barnes. The picture is of (most of) the course attendees and the faculty on the last day, it was raining, much like every day that week, so an indoor photo. It looks cool. Till next year!!

Just a reminder of the opening of applications for the EMBL postdoc scheme - EIPOD for 2012. Get in touch if you're interested in our draft project.

Licensing of data, and copyright is a complex thing, and always gets people hot under the collar! Some time ago, following consultation with our funders, we settled on a CC-BY-SA license for ChEMBL - this does a couple of things, but primarily it places an explicit license on the data so it is clear what you can do with it. There is a lot of hot air and active discussion over how 'public' and 'open' particular licenses are, but the CC-BY-SA 3.0 license made sense to us (for reference, this license is also used by the world's premier open resource wikipedia  - here is their license ) This license we apply to each release of the database, it makes the data freely available and usable. It requires attribution, so that users of derivative works know where the data comes from, can identify the funders and producers of the work - which we think is fair and appropriate, and finally it applies 'share-alike', so that if you distribute the ChEMBL data further yo...

We have an interdisciplinary postdoc project available as part of EMBL's EIPOD program (details here ). The project with is Matthias Willmanns based at EMBL Hamburg , and the appointee will spend time in both labs in a combined computational and experimental project aimed at discovering the mode of action of high-throughput screening hits from an anti-tuberculosis assay. Further details of the project are available here . This is deliberately brief, and candidates are meant to flesh out the project design as part of the application process. The deadline for applications is 5pm CEST 13th September 2012 .

ATC Code: G04BD (incomplete) Wikipedia: Mirabegron On June 28 2012, the FDA approved Mirabegron (tradename: Myrbetriq ; Research Code: YM-178), a novel, first-in-class selective β3-adrenergic receptor  agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. OAB syndrome is a urological condiction defined as urinary urgency, usually accompanied by frequency and nocturia , with or without urge urinary incontinence, in the absence of urinary tract infection or other obvious pathology. Mirabegron acts by relaxing the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of β3-receptor which in turn increases bladder capacity. Other treatments for OAB are already in the market and these include treatments with antimuscarinic drugs , such as Flavoxate (approved in 1970; tradename: Urispas; ChEMBL: CHEMBL1493 ), Oxybutynin (approved in 1975, tra...

'ChEMBL Is Alive' is to show that ChEMBLdb is a living database that is constantly being worked on by a number of people. As the Chemical Curator for ChEMBL, I (Louisa Bellis) thought it would be interesting for our Blog readers to find out what goes on behind the scenes at 'ChEMBL Towers' and to get regular updates on what we are doing to the data between releases and in response to user emails sent to chembl-help@ebi.ac.uk. As well as being the chemical curator, I also deal with most of the help-desk  traffic, where users can email in and let us know of any errors that they may have found, or even to suggest an improvement or enhancement for the interface. As an example of the work that is done to ChEMBL on an ongoing basis, I thought it would be good to give a brief summary of some of the chemical curation that occurred during the month of June 2012: An external user pointed out to me that they had come across a 'few' compounds that had the same ca...

As some of you may know, besides the ChEMBL web interface and the SQL dumps , there is a another way to access and retrieve data from your favourite public database, namely the RESTful web services . We have already provided API examples there using Java, Python and Perl but, as of today, we also provide examples for popular pipelining / workflow tools, such as Pipeline Pilot and KNIME . The user base of such tools is certainly growing, as they offer modularity, flexibility, transparency and higher integration and sharing capabilities compared to programming or standard software packages. In fact, demand for tighter integration between ChEMBL and these tools was one of the outcomes of our recent Workflows workshop . Indeed, using the web services via a workflow tool is a seamless way  to search, retrieve, integrate and analyse data without having to install, maintain and update local databases or write, dreaded for some, SQL queries. We have posted some useful examples ...

A reminder of an on campus, open, seminar from Andy Bell (now at Imperial College), detailing the discovery and development of UK-92,480 (also known as   sildenafil   and even better known as V1agra and R3vat10). Andy was one of the medicinal chemists and inventors on the PDE-5 inhibitor programme at Pfizer, and the story covers many aspects of drug discovery including, of course, the discovery of the side effect, and also one where the pharmacology led to many new molecular insights into NO signalling and PDE biology. There are many myths about the discovery of V1agra, so this is a rare opportunity to hear the exciting story first-hand. Here's Andy's abstract.... "Viagra™ (sildenafil) is a unique example of a chemical tool being used to discover the linkage between a biological mechanism and a disease through clinical trials. The presentation will describe the discovery of sildenafil and its use in defining the role of cGMP phosphodiesterases (particularly PDE5)...