• 2010 New Drug Approval - Pt. X - Ulipristal Acetate (Ella)



    ATC code: G03AD02

    The most recent approval by FDA is Ulipristal Acetate, approved on August 13th 2010 under the trade name Ella. Ulipristal Acetate (previously known by the research code CDB-2914 or VA-2914) is a progesterone agonist/antagonist emergency contraceptive, indicated for prevention of pregnancy following unprotected intercourse or known or suspected contraceptive failure.
    This drug is a selective progesterone receptor modulator (SPRM) with antagonist and partial agonist effects (a progesterone agonist/antagonist) at the progesterone receptor (PR, NR3C3) (Uniprot code: P06401). The Progesterone Receptor is a member of a very significant family of proteins for drug discovery, the Nuclear Receptors, a family of around 50 genes which are transcription factors, the transcription by NRs is usually ligand regulated. Ulipristal Acetate prevents progesterone, the endogenous ligand, from occupying its receptor. Ulpristal Acetate binds in the ligand binding domain (LBD) of PR (PFAM: PF00104).

    There are several structures known of PR complexed with ligands, a representative one is (PDB: 3D90). Ulipristal Acetate will compete with Levonorgestrel, another progestagen available on the market, which is approved for use up to three days post-intercourse as opposed to five days in the case of Ulipristal Acetate.
    Ulipristal Acetate is a small-molecule, natural product derived drug (Molecular Weight 475.6 g.mol-1), Rule-of-Five compliant and it is delivered as a tablet. Ulispristal Acetate is highly bound to plasma proteins (>94%), including high density lipoprotein, alpha-1-acid glycoprotein, and albumin. It is metabolized to mono- and di-demethylated metabolites, mostly by CYP3A4; the mono-demethylated metabolite pharmacologically active. Ulpristal Acetate shows high affinity for the related nuclear receptor - glucocorticoid receptor (GR, NR3C1). The terminal half-life of Ulipristal Acetate is ca. 32 hours. The recommended dosage is one tablet (30 mg) taken orally, with or without food, as soon as possible, within 120 hours (five days) after unprotected intercourse or a known or suspected contraceptive failure.
    The full prescribing information can be found here.
    The structure 17alpha-acetoxy-11beta-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione is a synthetic progestagen and is thus very similar to progesterone. Like other steroid hormones of this class, Ulipristal Acetate is characterized by its basic 21-carbon skeleton, i.e., four interconnected cyclic hydrocarbons with two methyl branches and a ketone. In this particular case, one of the methyl groups is replaced by a substituted aromatic amine. 
    NAME="Ulipristal Acetate"
TRADEMARK_NAME="Ella"
ATC_code= NA
SMILES="CC(=O)C1(CCC2C1(CC(C3=C4CCC(=O)C=C4CCC23)C5=CC=C
(C=C5)N(C)C)C)OC(=O)C"
InChI="InChI=1S/C30H37NO4/c1-18(32)30(35-19(2)33)15-14-27
-25-12-8-21-16-23(34)11-13-24(21)28(25)26(17-29(27,30)3)
20-6-9-22(10-7-20)31(4)5/h6-7,9-10,16,25-27H,8,11-15,17H2,
1-5H3/t25-,26+,27-,29-,30-/m0/s1"
ChemDraw=Ulipristal_Acetate.cdx
    The license holder is Laboratoire HRA Pharma.

  • MGMS Young Modeller Forum Meeting - December 10 2010, London, UK

    The MGMS have their annual Young Modellers Forum (YMF) meeting on December 10th 2010 at SOAS in London. Further details are here....

  • Research Code to Company Name Mapping


    As part of a long-term project connected with literature and web mining, competitor intelligence, and the history of drug development; here is a spreadsheet of research code stems, company name, country of company, and the name of the company when the research code stem was in use. It is incomplete, but still quite substantial with over 600 stems documented.

    Please feel free to download and use the spreadsheet in which ever way you please. If you find any errors, or can provide a longer list (as long as this is from Publicly available sources!) that would be fantastic. Any additions will be credited appropriately.

    So, Google docs is not currently working for me, but getting the list onto the blog itself, and therefore getting it indexed up in search engines, etc. was not too painful, so here is a link to an HTML table (sorted by company name).

  • USAN Watch - August 2010


    The August 2010 USANs have just been published, these are:

    USANResearch code Drug Type Drug ClassTarget
    AlvocidibFlavopiridol, HL-275, HMR-1275, L86-8275, MDL-107826A, NSC-649890Synthetic small moleculetherapeuticCDK inhibitor
    DanoprevirR05190591, RG-7227, ITMN-191Synthetic small moleculetherapeuticHCV Proteinase inhibitor
    LatrepiridineSynthetic small moleculetherapeuticComplex MOA
    LunacalcipolCTA-018Natural product-derivedtherapeuticVitamin D receptor
    MavrilimumabCAM-3001mAb therapeuticGMCSFr alpha-chain
    Moxetumomab pasudotoxCAT-8015, HA22mAbtherapeuticCD-22
    Semuloparin sodiumAVE-5026OligosaccharidetherapeuticAntithrombin III


    It may be of interest to note the USANs "Semuloparin" and "Semuloparin Sodium" in July and August this year. These USANs refer to the same active substance (Semuloparin), one being the sodium salt of the other. There are slight differences that exist between the WHO INN process and the USAN process. INNs do not include the salt/counterion in the name, whereas USANs historically have. Now, for USANs, both the salt and the parent molecule get assigned distinct USANs.

  • Deadline for ESPOD Project on Malaria Target Discovery Is Approaching....


    A reminder that the deadline for the application for the EMBL-EBI/Sanger ESPOD fellowships is fast approaching - including that for the 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!

  • ChEMBL Resources for Drug Discovery Course - Feb 2011


    We have penned into our diaries the dates of Monday February 14th 2011 thru Friday February 18th 2011 for the second ChEMBL residential training course. This will be held on campus here at Hinxton, registration and details of the sessions to be covered will appear on the EBI website shortly.

    2010 year was our first course, and we had to prepare a lot of material, etc. but we really enjoyed it, and the 2011 course will be even better.

    The image above is from the excellent xkcd.

  • From One Of Our Collaborators - MoSS+ChEMBL with Bioclipse

    “Pharmaceutical Knowledge Retrieval through Reasoning of chEMBL RDF” is the title of my master thesis, a twenty-week research project performed at the Department of Pharmaceutical Bioscience at Uppsala University (Prof. Wikberg, supervised by Egon Willighagen). The project aims at using the ChEMBL data with a technology that might be new to some: by using semantic web technologies. The life sciences workbench Bioclipse (doi:10.1186/1471-2105-10-397) has support for several semantic web tools, including RDF, and was used to establish such a connection.

    Two aspects were looked at in this study. Firstly, we developed the search functionality for ChEMBL data to use RDF. For this, we took advantage of the RDF-ized ChEMBL knowledgebase (using the data from ChEMBL 02). Secondly, we developed a use case where compounds derived from ChEMBL are analyzed with the substructure mining software MoSS (see the Bioclipse Wiki). Here, we search for common and discriminative substructures within or between kinase families.

    Within the context of these two aspects, we developed an application using both the JavaScript and the Wizard functionality in Bioclipse. The above shown wizard shows how various searches for compound-protein interaction can be formulated. Results are shown in the "Results table". The user can then select which data he wants to save, by moving it to the lower table which lists the data that will be saved by this wizard.

    A second, more application-targeted Wizard was developed that primarily concentrates on retrieving compounds that bind proteins in a certain kinase family with a given activity type (see below). A histogram can be opened to visualize the distribution of activities. Lower and upper bound values can be selected, for focus, for example, only on that active compounds. A second, identical wizard page is provided to select a second dataset. This allows the user to set up a between-family data set. The saved data can then be used in the MoSS application to find the common and discriminative substructures (not shown).


    Benefits of this approach focus on the data interoperability: the RDF technologies are used as uniform and Open Standard access to the ChEMBL data. Using this approach, implementing new search queries is very easy, and does not require one to know anything about the database schema; a common controlled vocabulary (ontology) hides those implementation details. Community standards for such vocabularies are under development, and will integrating the ChEMBL data with other databases and other applications.

    Does this sounds interesting to you, or do like to give us feedback? Please send a note to annzi.andersson+chembl@gmail.com . Further details are provided in my blog!

     Sincerely, Annsofie Andersson.

  • Webinar - Installation and setup of a MySQL instance of ChEMBL



    We are planning to run a web tutorial on the installation and set-up of a local MySQL version of ChEMBL. This will allow very flexible querying of the data within ChEMBL (with the exception of chemical structure searching for which there is currently no freely available cartridge/plugin (yet)). We will do an entire download and install of MySQL, download of the ChEMBL data, and setting everything up, then doing some sample queries - all within one hour.

    The web meeting will be from 3pm to 4pm UK time (we are on BST at the moment) on Thursday 5th August. Please mail us if you want a link to the web-meeting, and the toll-free dial-in number. Please, (please), do not edit the title on the mail message link.