• Some Summer Reading - The Ultimate Inferior Beings by Mark Roman


    I usually only manage to read one fiction book a year - this is pretty pathetic I know, but this year I have already chosen the one book, and I'm actually quite excited about it - The Ultimate Inferior Beings by Mark Roman.

    An unlikely prophecy, a neutrino bomb, and a demented alien with a ‘Messiah’ complex herald the end of the Universe. When jixX is appointed spaceship captain for a dangerous space mission he doesn’t regard it as a promotion. More like a computer error, given he’s a landscape architect. The error theory gains in strength when he meets the crew: a carpenter, a gynaecologist and a scientist trying to prove the existence of God. To add to jixX’s woes, there’s a stowaway on board, one of his crew is a saboteur and the ship’s computer thinks it’s a comedian. And then they meet aliens. Not technologically advanced aliens - their civilization is based on the invention of the brick - but jixX has a bad feeling about them anyway. Among them are a religious bunch who believe in The Ultimate Inferior Beings - a species that are really, really bad at everything. According to an ancient prophecy this species will, perhaps inadvertently or absent-mindedly or through some tragic mishap, bring about the end of the Universe. One alien becomes convinced that the humans are these incompetent beings. He realizes he must be the Chosen One, and that it is his Duty to wipe them out before they can trigger total annihilation. So it comes down to jixX to save Humankind...

    Sounds great doesn't it?

    The author may well be strangely familiar (more precisely, strange and familiar) to many of the ChEMBL-og readers ;)

    PS There's now a YouTube video trailer for the book.

  • Canadian Bioinformatics Workshop

    Yesterday, I gave a tutorial in Toronto, Canada on how to use the EBI chemical entities databases as part of the 'Patent Informatics: Sequence & Chemical Databases for Prior Art Searching' workshop. This one day session was organised by the Canadian Bioinformatics Workshop. It was held at the Ontario Institute for Cancer Research, which is situated in downtown Toronto. It was a very well organised workshop with good facilities and tasty refreshments. Toronto is a beautiful city and I hope to explore it tomorrow before flying down to Boston to give my talk at Bio-IT World.

  • New Drug Approvals 2012 - Pt. IX - Florbetapir F 18 (AmyvidTM)






    ATC code: V09AX05 (incomplete)


    On April 6th, FDA approved Amyvid (Florbetapir F 18), a radiolabeled intravenous imaging agent for the differential diagnosis of Alzheimer's Disease.

    Alzheimer's Disease (OMIM 104300, MeSH D000544) is a non-treatable, progressively worsening and fatal disease and the main cause of dementia.
    Most commonly affecting the elderly (>65y), it correlates with the growing deposits of aggregating beta amyloid (UniProt P05067) fibrils in the brain, eventually physically destroying it, and abnormal aggregation of the tau protein (UniProt P10636), a microtubule-associated protein inside neurons.
    Early symptoms of Alzheimer's include impairment of short term memory, advanced ones, irritability, confusion, aggression, mood swings, and long term memory loss, amongst others.

    Diagnosis of Alzheimer's is complicated by overlap of symptoms with other cognitive diseases, and "normal" signs of ageing; sometimes, only brain autopsy (necessarily posthumous) can confirm its presence, while, conversely, patients displaying typical Alzheimer's symptoms sometimes don't show its physiological manifestation. Differential diagnostic techniques include detection of (amongst other biomarkers) amyloid or tau proteins in the spinal fluid, and brain imaging using Positron Emission Tomography (PET), with or without contrast enhancing agents, i.e. radionuclides. A drawback of an early such compound, Pittsburgh compound B (PiB, ChEMBL ID CHEMBL207456, PubChem 2826731), is the short half life (~20 minutes) of the carbon isotope (11C) included. Florbetapir, on the other hand, has a radioactive fluorine isotope (18F) with a half life of ~2 hours, improving its handling and signal strength.

    It has to be noted that the presence of plaques, e.g. visualized by PET, and potentially aided by Florbetapir, does not necessarily and sufficiently indicate Alzheimer's; plaques may be present in patients with other neurological disorders, or elderly people with normal cognition. However the absence of significant plaques may rule out the possibility of a patient suffering from Alzheimer's.


    Florbetapir (ChEMBL ID CHEMBL1774461, PubChem 24822371) is a radiocompound with molecular weight 360.4 Da, ALogP 3.14, 1 hydrogen bond donor, 4 hydrogen bond acceptors, and thus fully rule of five compliant. It possesses a radioactive isotope of fluorine, 18F, and a C=C double bond in trans / E configuration.
    Its systematic (IUPAC) name is 4-[(E)-2-[6-[2-[2-(2-fluoranylethoxy)ethoxy]ethoxy]pyridin-3-yl]ethenyl]-N-methylaniline, Canonical SMILES CNc1ccc(\C=C\c2ccc(OCCOCCOCC[18F])nc2)cc1, Standard InChI=1S/C20H25FN2O3/c1-22-19-7-4-17(5-8-19)2-3-18-6-9-20(23-16-18)26-15-14-25-13-12-24-11-10-21/h2-9,16,22H,10-15H2,1H3/b3-2+/i21-1.

    After injection of Amyvid as a single recommended dose of 370 MBq, the agent passes the blood brain barrier and accumulates at amyloid plaques in the patient's brain. 30 to 50 minutes post injection, a 10 minute PET image is acquired.

    It is unknown whether Amyvid affects reproductive capacity or causes fetal harm, or whether it is secreted in human milk, but it is not recommended to be used in the respective population. The agent is not indicated for use in pediatric patients. Majority of clinical studies subjects being elderly, no overall differences in safety or effectiveness between them and younger subjects were observed. Because of the agent being radioactive, special precautions have to be taken retrieving, transporting, and administering the agent. The radiation absorbed dose from a single Amyvid dose is 7 mSv in an adult and thus comparable to a chest CT scan, or about twice the normal yearly background dose.
    Notable adverse reactions include headache (<2% of patients), musculoskeletal pain, fatigue, nausea (<1%), and anxiety, back pain, increased blood pressure, claustrophobia, feeling cold, insomnia, and neck pain (<0.5%). In early 2011, FDA recommended against approval of Florbetapir, unless structured training programmes for PET readers using Florbetapir would be provided; latest clinical trials of Florbetapir include data from readers either trained manually, or electronically, both proving to be effective.

    Amyvid has been developed by Eli Lilly and Company, and Avid Radiopharmaceuticals Inc., its wholly owned subsidiary, and is marketed by Lilly.

    The full prescribing information can be found here.



  • ChEMBL Workflows for medicinal chemists workshop






    On Friday 11th May 2012 we are running a small (and free) interactive workshop on "Shaping the Future of ChEMBL".  We would like your input to develop some easy to use workflows for several key tasks that drug discoverers often want to do, and could do more efficiently with the ChEMBL data.  These workflows would be aimed at medicinal chemists and would cover the use of ChEMBL data in lead generation and optimization tasks, hence we would like to involve medicinal chemists in their creation and implementation.  

    The workshop will be on campus here at Hinxton, and will start around 10am and finish around 3pm (lunch, coffee and cakes will be provided).

    If you are interested in helping, with what will hopefully be a fun day, please contact us.

  • Interface & Searching Webinar 18th April

    This is a call for people wanting to sign up for the "Interface & Searching" webinar that will be hosted next Wednesday 18th April at 3.30pm (GMT).
    It will be a 45 minute webinar that will take you through the ChEMBL interface and schema, showing you how to navigate the data and how the tables are all connected.
    Remember to register your interest in our webinars on the Doodle Poll. Make sure that you leave your **email address** as well as your name so that we can send the connection details to you. Any problems, please contact chembl-help@ebi.ac.uk.
    For those of you who can't make it to this webinar, we will be hosting it again on the 13th June.

  • USAN Watch - April 2012


    The USANs for April 2012 have just been published.


    USAN Research Code StructureDrug ClassTherapeutic classTarget
    alirocumabREGN-727, SAR-0236553mAbtherapeuticPCSK9
    birinapantTL-32711synthetic small moleculetherapeuticIAPs
    bevenopranCB-5945synthetic small moleculetherapeuticmu opioid receptor
    camicinalGSK-962040B

    		synthetic small moleculetherapeuticmotilin receptor
    cindunistatPHA-84250, SC-084250, PF-00572986    synthetic small moleculetherapeuticNOS?
    danirixinGSK-1325756B   synthetic small moleculetherapeuticCXCR2
    demcizumabOMP-21M18   mAbtherapeuticDLL4
    elubrixin, elubrixin tosylateSB-656933-AAF, SB-656933-AAA  synthetic small moleculetherapeuticCXCR2
    etirinotecan pegol, etirinotecan pegol tetrahydrochloride, etirinotecan pegol tetratriflutateNKTR-102   natural product-derived small molecule therapeutictopoisomerase 1
    fasinumabREGN-475, SAR-164877    mAbtherapeuticNGF
    lomibuvirVX-222   synthetic small moleculetherapeuticHCV NS5B polymerase
    mafodotinmc-MMAF, mcMMAF, SGD-1269, monomethyl auristatin F

    		peptidetherapeutictubulin
    neceprevirACH-0142684   synthetic small moleculetherapeutic
    pexastimogene devacirepvecJX-594   virustherapeutic
    rabusertibLY-2603618   synthetic small moleculetherapeuticCHEK1 CHEK2
    rilimogene galvacirepvecProstvac-V   virustherapeutic
    sebelipase alfaSBC-102   enzymetherapeutic
    vercirnonGSK-1605786, CCX-282   synthetic small moleculetherapeuticCCR9
    vintafolideEC-145   natural product-derived small moleculetherapeuticFolate Receptor, tubulin
    vorsetuzumabSGN-70mAbtherapeuticCD70
    vorsetuzumab mafodotinSGN-75 mAb ADCtherapeuticCD70

    I knocked this together during a meeting ( :O ) so there may be some errors, feel free to add more detail/corrections in the comments.

    A couple of extras have appeared on the USAN web page recently.... so I've updated the table above appropriately. Well, two more have appeared on the USAN site! Will add these soon. It looks like there are some subtle rejigging of the business rules for USANs - in particular the assignment of a USAN for the drug conjugate mafoditin - I do wish that the USAN office would reply to emailed questions.....

  • Joint EMBL-EBI and WT Resources for Computational Drug Discovery Course - 2-6 July 2012


    This joint EBI-Wellcome Trust course aims to provide the participants with the principles of chemical biology and how to use computational methods to probe, explore and modulate biological systems using chemical tools. The course will be comprised of a mixture of lectures and hands-on components. The conceptual framework will be covered, as well as direct practical experience of retrieving and analysing chemogenomics data. Participants will be able to do their own target analysis and identify appropriate chemical tools for probing biological systems of interest to them.

    Check out more details on the link above.


  • Some New GPCR Structures (Coming)


    I still get excited when a new set of interesting coordinates get released in PDBe - I hope I never stop getting this thrill from ~300 Kbytes of 3-D coordinates. Anyway, I'm packing my bag to return from an excellent conference/advanced school in Brazil, and I thought I'd spend a little time browsing some of my regular sites. One of these was the GPCR Network page, and it looks like there are two more GPCR structures to be released soon (or at least solved)!! It's such a tease to have an image of the structures on that page - so now I'll be regularly checking the usual suspect journals for the pre-press papers.....

    The new ones appear to be the Nociceptin receptor (UniProt:P41146), and the Muscarinic M1 receptor (UniProt:P11229). Note I don't know that the structures are of the human receptor, but the UniProt links are for the human orthologue).

    Can't wait.