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...

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

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. ...

Following the success of our ChEMBL Bot , there is now a new faithful bot out there which answers to the name  @MalariaSARLit and is looking for new followers. Its job is to tenaciously monitor PubMed for new malaria-related publications, score them according to our ChEMBL-likeness score and tweet a ChEMBL-like one daily at noon GMT. Followers of the bot will get a  free and reliable antimalarial SAR paper alert every day in their twitter feed.   George (NKOTB fan)

Here's a paper detailing some multi-method target prediction work as part of the GeMoA FP7 project. Proud, as ever, to publish Open Access. %A Martínez-Jiménez F %A Papadatos G %A Yang L %A Wallace IM %A Kumar V %A Pieper U %A Sali A %A Brown JR %A Overington JP %A Marti-Renom MA %D 2013 %T Target Prediction for an Open Access Set of Compounds Active against Mycobacterium tuberculosis %J PLoS. Comput. Biol. %V 9 %P e1003253 %O doi:10.1371/journal.pcbi.1003253 jpo

We are very pleased to announce that a new release of the malaria-data resource (MMV_2) is now freely available  here .  The release was prepared on 1st March 2013 and contains: 362,845 compound records 280,985 compounds 3,288,801 activities 190,243 assays 5,431 targets 24,200 documents The database contains several new datasets, including OSDD , Harvard and WHO-TDR Malaria screening data.  Furthermore, the new interface has adopted the new look and feel features recently introduced  in the main ChEMBL interface, such as the redesigned search hits tables and document report card. As usual, the interface provides compound, assay and target keyword search capabilities, as well as structure-based and sequence-based search functionality for compounds and protein targets respectively. Finally, structure look-ups are offered out-of-the-box via the UniChem cross-references.  Please see MMV_2_release_notes.txt for full details of al...

Many of the readers of the ChEMBL-og are interested in drug discovery against neglected and rare diseases. One of the great things for us in this field is the opening up of data in this field - there was the almost simultaneous release of primary HTS data from GSK, Novartis & St. Judes in 2011, more recently the results of a GSK HTS for TB. Having this data publicly available, for all, means that many smart people can analyse the data, and of course, pooling data in this way effectively is equivalent to running the assay against a far larger compound set, and allows more powerful cheminformatics analysis to identify chemical series, preliminary SAR, etc . Many of these datasets are available in our ChEMBL-NTD and ChEMBL-Malaria archives - and we know 2013 will be a great year for more data just like this! All these data are available for download, in the exact form as supplied by the depositor, no accounts/passwords, no lock-in to a software infrastructure, with no restrict...

The Drugs for Neglected Diseases initiative (DNDi) and Medicines for Malaria Venture (MMV) announce today the identification of three chemical series targeting the treatment of deadly neglected tropical diseases (NTDs), through DNDi’s screening of MMV’s open access Malaria Box. The resulting DNDi screening data are among the first data generated on the Malaria Box to be released into the public domain, exemplifying the potential of openly sharing drug development data for neglected patients. The open access Malaria Box is an MMV initiative launched in December 2011 to catalyse drug discovery for malaria and neglected diseases. It contains 400 molecules, selected by experienced medicinal chemists to offer the broadest chemical diversity possible and is available free of charge. In return, MMV requests that any data gleaned from research on the Malaria Box are shared in the public domain within two years. To date, more than 100 Malaria Boxes have been delivered to over 20 count...

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 .

The Teach-Discover-Treat (TDT) initiative was launched at the ACS meeting in San Diego under the umbrella of the Computers in Chemistry Division. The slides that describe the initiative are available on the website www.teach-discover-treat.org TDT aims to address outstanding gaps in drug discovery education and treatments for neglected diseases. A competition was launched that solicits submissions of computational models and tutorials for drug discovery for neglected diseases. All tools used for the computational workflows must be freely available (open source, free web servers, free download of executables) to enable global collaboration and innovation. There are 4 categories in the competition, and 4 awards!   Three of the categories are focused on specific neglected diseases for which datasets have been provided. Specific requirements have been formulated for the workflows that are to be the submissions for the competition in these three categories. Th...

I've just spent a great week in Cape Town , at UCT , visiting the lab of Kelly Chibale ; where there's lots of activity in academic drug discovery, and also at the Institute of Infectious Disease and Molecular Medicine . My first time in Africa, and it won't be my last!

We're delighted to announce the availability of three distinct new datasets on the ChEMBL-NTD portal , available for download, reuse, etc. These are: Novartis-GNF Malaria Liver Stage dataset (associated with this Science publication) ( Plasmodium falciparum ). DNDi Human African Trypanosomiasis (HAT) dataset ( Trypanosoma brucei ) DNDi Chagas Dataset ( Trypanosoma cruzi ). Further details of the assays and compounds are to be found on the ChEMBL-NTD portal . The data will be integrated and loaded into a future version of ChEMBL, as well as the direct data download links. Once more, we thanks the depositors, DNDi and Novartis-GNF , for their benevolence and commitment to Open Science. The associated publication for the Novartis-GNF dataset is: %T Imaging of Plasmodium Liver Stages to Drive Next-Generation Antimalarial Drug Discovery %A S. Meister %A D.M. Plouffe %A K.L. Kuhen %A G.M.C. Bonamy %A T. Wu %A S.W. Barnes %A S.E. Bopp %A R. Borboa %A A.T...

Just a quick (but surprisingly wordy) follow up on the previous post on the drug profiling against malaria. Drug repurposing/reuse/rescue offers great potential for the enhancement of patient lives and also is a quick way of pushing new therapies through the clinic. It is often see as low cost and low risk, is highly translational in terms of the research, and there are some stunning success stories. It is therefore very sensible to screen known drugs in assays of interest, which is exactly what was done in the recent, excellent, Science paper. The compounds in Table 1 of the paper are reported at the highly active set (and these exclude already known established antimalarial drugs which all pass the selection criteria used for compounds in this table, this seems a pretty good and pragmatic place to set cutoffs). For use as an widely-used and developing world-applicable antimalarial (co)-therapy I would have imagined that ideally you would want established well tolerated daily dosi...

There's a really interesting paper just published in Science on the screening of the NCGC drug collection against the malaria parasite, it's a tour de force in the application of screening and genomics analysis/exploration of bioactivity data. Amongst the 32 highly actives there are mostly cytotoxic agents, which are probably no big surprise, but a couple of interesting things in there, more later on this (probably...) Anyway the paper is here . %T Chemical Genomic Profiling for Antimalarial Therapies, Response Signatures, and Molecular Targets %J Science %V 333 %P 724-729 %D 2011 %A J. Yuan %A K.C.-C. Cheng %A R.L. Johnson %A R. Huang %A S. Pattaradilokrat %A A. Liu %A R. Guha %A D.A. Fidock %A J. Inglese %A T.E. Wellems %A C.P. Austin %A X.Z Su

World Malaria Day for 2011 is on April 25th again this year - see the worldmalariaday website for more details. Also look at the ChEMBL-NTD website for some relevant data from the ChEMBL resources.

We are speaking at a training school on the prioritisation of drug targets for neglected diseases running from May 16th to May 21st 2011, held at the University of Siena, Italy. It is organised under Working Group 1 of COST Action CM0801. Here is some text from the course brochure (which can be found here ) This training school was conceived to teach and train researchers on the currently available tools that may lead to drug target identification and prioritization, before moving to their validation in vivo . The course will consist of lectures and practical classes. In guided hands-on computer sessions all participants will analyze sequence, structure, and function of unknown sequences. By that they will learn about the existence as well as the source and availability of bioinformatics software and how to apply these tools and interpret results with confidence. The school will provide computers to all trainees. All lectures will be in English. Spaces are limited, and the deadli...

Here is an update on some follow-on chemistry on the GSK Malaria screening set , provided by the researchers at GSK's Tres Cantos Medicines Development Campus . Chemistry in progress TCMDC-123822, TCMDC-123823, TCMDC-123824, TCMDC-123827, TCMDC-134513, TCMDC-123579, TCMDC-123582, TCMDC-125454, TCMDC-134141, TCMDC-134142, TCMDC-134143, TCMDC-134692, TCMDC-135254, TCMDC-135271, TCMDC-135426, TCMDC-135461, TCMDC-135462, TCMDC-135463, TCMDC-135554, TCMDC-135654, TCMDC-135655, TCMDC-135656, TCMDC-135657, TCMDC-135677, TCMDC-135687, TCMDC-135789, TCMDC-135796, TCMDC-135816, TCMDC-135911, TCMDC-136013, TCMDC-136014, TCMDC-136015, TCMDC-136016, TCMDC-136051, TCMDC-136060, TCMDC-136134, TCMDC-136185, TCMDC-136188, TCMDC-136303, TCMDC-139046 Chemistry on hold TCMDC-123540, TCMDC-123620,...

A reminder that the deadline for the application for the EMBL-EBI/Sanger ESPOD fellowships is fast approaching - including that for t he exciting Overington/Rayner malaria project - (the final date for applications is August 15th 2010 in fact). So if you are interested, please send in your completed application!

A number of you have asked for further details on the malaria postdoc project.... (details on how to apply, deadlines, etc can be found here ). Malaria remains one of the most significant causes of developing world mortality, and this global burden coupled with recent reports of parasites resistant to artemesinin, the most recently released anti-malarial, makes the search for new therapeutics an urgent priority. While the availability of multiple Plasmodium genome sequences has the potential to make a significant impact on malaria drug development, almost all previously successful therapies were empirically discovered and developed, and without a defined molecular target. Such entirely empirical-based discovery is now not considered practical, and so a hybrid approach of cell-based screening followed by target discovery for bioactive hit series is a compelling and practical way forward. Recently a number of very significant disclosures of HTS cell-based screening studies have occurr...

There is an opportunity to apply for a Postdoc. position under the joint supervision of John P. Overington (EMBL-EBI) and Julian Rayner (Sanger Centre). The project will use the recently published and publicly released HTS Malaria datasets , and attempt to predict and validate target assignments using a variety of computational and experimental approaches. The position would ideally suit an ambitious and skilled researcher interested in chemical and molecular biology. The deadline for applications is 15th August 2010 . Further details and the application process can be found here and here . I'd be happy to clarify anything about the project, just mail me.