The ChEMBL-og

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.

Registration is now open on the LinkedIn ChEMBL User Group page for our first meeting. If you are not on LinkedIn and would still like to come, please mail me . To parents of young children the world over (in 175 territories in fact) the image above will be too familiar.

ATC code:L01XC11 On 25th March 2011, the FDA approved Ipilimumab (trade name  Yervoy TM , ATC code:L01XC11), a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody indicated for the treatment of unresectable or  metastatic  melanoma. ( Melanoma ;  CRUK melanoma ; OMIM:  155600 ; ICD:  C43 ). Malignant melanoma is diagnosed in an estimated 160,000 new patients each year and, despite being less common than other skin neoplasms, it is responsible for 75% of skin cancer-related deaths. Current available treatment options for melanoma are limited to surgery, chemotherapy, radiotherapy and immunotherapy, although there are a number of targetted agents in the clinical development at the moment. Ipilimumab effect in melanoma is indirect and probably due to enabling a T-cell mediated immune response In a randomised clinical study that assessed the response of unresectable or metastatic melanoma patients to Ipilimumab, alone and in combination with investigational peptide vacc

This Network will establish an Academia-Users Network in Chemical Biology to initiate, establish and nurture collaborative projects for the advancement of the drug discovery process. It aims to expand the capability of UK drug discovery, with new drug targets, new tools to validate targets and new multidisciplinary partnerships to explore the platforms, tools and targets of the future. A poster for this new network is above, but a website is being set-up for this, and as soon as it is ready to go, we'll provide links on the ChEMBL-og. The network is funded by the  EPSRC ,  BBSRC  and  MRC , funded through their joint “Collaborative Networks in Chemical Biology” initiative.

There's a great looking conference in Budapest this August, the 4th European Conference on Chemistry for Life Sciences (4ECCLS) - a link to the conference website is  http://www.4eccls.mke.org.hu/

There is an excellent description of specific subtypes of monoclonal antibodies on Wikipedia, these can be easily incorporated into the Drug_Class section of our drug taxonomy. Specifically as Drug_Type_Subsubclass. An interesting property of this classification is that it should be possible to write an algorithm that classifies arbitrary sequences against this taxonomy. mab - whole monoclonal antibody. Fab - fragment, antigen-binding (one arm). F(ab')2 - fragment, antigen-binding, including hinge region (both arms). Fab' - fragment, antigen-binding, including hinge region (one arm). scFv - single-chain variable fragment. di-scFv - dimeric single-chain variable fragment. sdAb - single-domain antibody. 3funct - trifunctional antibody. BiTE - bi-specific T-cell engager. Other - an antibody like drug that does not fit one of the above classes.

We now have an immediately available position within the ChEMBL group for an exciting project looking at data integration of ADMET data alongside structural and comparative genomics data. This role requires good general bioinformatics knowledge, programming in perl (or equivalent), knowledge of SQL, and database querying and data integration. Previous experience with ADMET data would be beneficial. More details are  available on request .

BioCatalogue is a registry of Web Services in the biosciences. All the ChEMBL web services (including the REST and SOAP PSICQUIC) services are now listed in BioCatalogue .

ATC code : V08CA09 On March 14 th 2011, the FDA approved Gadobutrol (USAN: Gadobutrol USANdate: 2010 tradename: Gadavist  NDA 201277), a gadolinium-based contrast agent, for intravenous ( i.v. ) use in diagnostic MRI to detect and visualize areas with disrupted blood brain barrier and/or abnormal blood supply of the central nervous system. In MRI, when an electromagnetic field is applied, the hydrogen nuclei present in the body, flip their spin and align with the direction of the field. Once the field is turned off, the hydrogen nuclei decay to the original spin-down state and release a photon, corresponding to the energy difference between the two states. Since, hydrogen nuclei in different tissues return to their equilibrium state at different rates, a distinctive image can be obtained. Gadobutrol enhances the contrast in MIR images, by decreasing the spin-lattice relaxation time (T 1 ) and the spin-spin relaxation time (T 2 ). The gado- USAN/INN stem

We plan to run some webinars detailing recent progress and changes with some of our services. The first will be a webinar on the ChEMBL REST web services and programmatic access at 3 pm BST on 31st March 2011. Please mail to register for this. The second will be a webinar on the current ChEMBL schema at 3pm BST on 30th March 2011. Please mail to register for this. Please note that at this time of year, not all countries are synchronised on the transition to Daylight Savings time (if indeed they do change). Please check mapping of your local time to BST. Please, please try and resist the temptation to edit the subject lines of the mail links above.

We have a visitor to the EBI on 6th April 2011 -   Jens Loesel from Pfizer , Sandwich. Jens will give a talk at 1pm on some large-scale cheminformatics analysis of the Pfizer screening file that he has done. If any off campus people want to come to the talk, they are very welcome; but I will need a name and affiliation to get them past security - mail me . An abstract for the talk is below.... MedChem Attractiveness and Redundancy -  Looking for value in Compounds and Chemical Space Jen Loesel, Pfizer A more diverse screening file is a better screening file. A bigger screening file is a better screening file. Are these statements really true? We will critically scrutinize both these questions in the talk. In part 1 we will investigate the quality of chemical structures. A good screening file needs to balance quality versus diversity. We generated an algorithm that is purely based on structure to achieve this. The algorithm is able to compete with medicinal chemists in ranking t

ATC code : L04AA26 On March 9th, 2011, the FDA approved Belimumab (trade name: Benlysta , ATC code L04AA26 ), an immunosuppressant human monoclonal antibody, for treatment of patients with systemic lupus erythematosus ( SLE , OMIM: 152700 , ICD-10: M32. ), a systemic autoimmune disease . The prevalence of SLE varies among differing ethnic groups, and countries, e.g. 40 per 100,000 in Northern Europe, 53 in 100,000 in the US, and 159 in 100,000 among people of Afro-Caribbean descent; this translates to about 159,000 cases in the US, among 1.5 million cases of different forms of lupus in general. In SLE, periods of illness alternate with remissions, and symptoms are diverse, comprising fever, malaise, joint pains, myalgias, and fatigue, but also dermatological symptoms ( e.g. malar rash ), anemia, cardiac, pulmonary and renal impairments as well as neurological and neuropsychiatric syndromes such as headache and depression, rendering diagnosis challenging. SLE is currentl

The next area for consideration in our descriptive taxonomy for drugs is stereochemistry . There are many differing types of stereoisomers encountered in general chemistry, and the area is complex, but the majority of these are not relevant for drug discovery; for example atropisomers , although an important effect is not important for among drug substances. The most significant category of stereochemistry for drug like molecules involves chiral centers at sp 3 hybridised carbon atoms connected to four chemically distinct atoms (often giving rise to  enantiomerism ). Another relevant case of stereoisomerism for drugs are  diastereoisomers , these are stereoisomers that are not enantiomers, and include cis -/ trans - ( E -/ Z -) configuration of alkenes. So for Drug_Stereochemistry_Class , a drug can be: Chiral - containing a single defined stereoisomer of the drug substance, and which lacks an internal plane of symmetry. Racemic - containing a mixture of stereoisomers of the d

It is intuitive to describe what a drug is in natural language - a small molecule, etc , but one problem is that these descriptive terms are context dependent, loosely defined and are used very variably across the literature; and so when someone asks 'How many small molecule drugs there are?' - first of all it depends on what is a 'drug', and secondly what is a 'small molecule'. As far as I can tell there is not a descriptive taxonomy for drugs (I use the term taxonomy here as a bridge term between a controlled vocabulary / dictionary and an ontology ). For our own purposes within ChEMBL we need such a taxonomy, but post our initial thoughts here for comment, and no doubt (and hopefully), significant correction and improvement (use the comment section of the blog, then everyone can see any discussions). Drugs are regulated products that are 'intended use in the diagnosis, cure, mitigation, treatment or prevention of disease' - let's not visit

ATC code: R03DX07 On February 28th, 2011, the FDA approved Roflumilast (tradename: Daxas tradename: Daliresp  NDA 022522) for the treatment of patients with chronic obstructive pulmonary disease ( COPD ) a chronic and serious disease involving restriction of full lung function. The narrowing of airways of COPD is irreversible, and follows inflammation in the lung, believed to be linked to environmental pollutants such as tobacco smoke, workplace dusts and urban air pollution. This inflammation causes structural damage to the delicate alveoli structures. Roflumilast and an active metabolite, Roflumilast-N-Oxide, are selective Phosphodiesterase 4 inhibitors. The subfamily of Type 4 Phospodiesterases comprises four distinct members, PDE4A, -4B, -4C, and -4D (Uniprot: P27815 , Q07343 , Q08493 , Q08499 , respectively, all are very closely related enzymes containing a characteristic cyclic nucleotide diesterase catalytic domain Pfam: PF00233 ). These in turn occur in differe

The deadline for applications for the 2011 intake for EIPODs (interdisciplinary postdoc fellowships within EMBL, funded by EMBL and Marie Curie Actions) is approaching soon - 20th March 2011 to be specific. There are lots of interesting predefined projects, but also the opportunity to define your own collaborative project between EMBL faculty in different units. The ChEMBL group are involved in two predefined projects 1) NGS methods for natural product profiling/discovery and 2) text mining approaches for clinical candidate discovery from the literature.

partial ATC code: C09CA The most recent FDA drug approval is Azilsartan Medoxomil, approved on February 25th (NDA 200796). Azilsartan Medoxomil (research code: TAK-491; tradename: Edarbi ) is an angiotensin II receptor blocker prodrug indicated for the treatment of hypertension, either alone or in combination with other antihypertensive agents. Hypertension is a medical condition in which the blood pressure in the vessels is too high, and can lead to kidney failure, stroke, myocardial infarction (heart attack), aneurysm, and many other pathologies. The renin-angiotensin system is a key regulator of blood pressure; Angiotensin is an hormone system that regulates the blood pressure and the fluid balance. The short peptide Angiotensin II is the principal agent of this system, and is responsible for vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Azilsartan (ChEMBL: ChEMBL57242 ; PubCh

We are collaborators on a paper just published in Nature Reviews Drug Discovery , investigating the relationship of in vitro and physicochemical data and ADMET properties, as you will imagine, a lot of the underlying data for this work and analysis came from the ChEMBL database. There is quite a lot of new stuff in there... %J Nature Reviews Drug Discovery %V 10 %P 197-208 %D 2011 %O doi:10.1038/nrd3367 %T Probing the links between in vitro potency, ADMET and physicochemical parameters %A M.P. Gleeson %A A. Hersey %A D. Montanari %A J. Overington

We are pleased to announce the release of the ChEMBL RESTful Web Service API ( application programming interface ). The first release provides the functionality to support programmatic retrieval of ChEMBLdb compound, target, assay, and bioactivity data. In the coming weeks and months we will extend the feature set of the REST API to support: Searching of compounds with SMILES, InChI keys, including substructure and similarity searches Searching of targets by protein identifiers Retrieval of results in JSON format We have provided a documentation page that describes the API functionality in more detail and also describes how to get started with using our java client to access API: https://www.ebi.ac.uk/chembldb/index.php/ws . Sample urls: Retrieve a compound record - https://www.ebi.ac.uk/chemblws/compounds/CHEMBL1 Retrieve a target record - https://www.ebi.ac.uk/chemblws/targets/CHEMBL2477 Retrieve an assay record - https://www.ebi.ac.uk/chemblws/assays/CHEMBL1217643 As alw