ChEMBL Resources

Resources:
ChEMBL
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SureChEMBL
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ChEMBL-NTD
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ChEMBL-Malaria
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The SARfaris: GPCR, Kinase, ADME
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UniChem
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DrugEBIlity
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ECBD

Wednesday, 28 July 2010

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.

Tuesday, 27 July 2010

From One Of Our Collaborators - CanSAR


One of our collaborators, Bissan Al-Lazikani is building a highly integrated system for cancer target and drug discovery - canSAR. A pre-release of the Target and Drug Synopsis pages is now available, populated with the Genomics of Drug Sensitivity Project at the Wellcome Trust Sanger Institute, canSAR complements the annotation of the 1000 cell-line screening project.

Due to the pre-release nature of this component of canSAR, many features have been disabled and removed. The full public release of canSAR will be available later in the year (it is very cool though!).

canSAR is developed and hosted by the Cancer Research UK Centre for Cancer Therapeutics at the Institute of Cancer Research.

Sunday, 25 July 2010

Interest in a ChEMBL User Group (ChUG) meeting?

We are now amassing a reasonably sized group of users for the ChEMBL database, both for the web interface, SARfari and local install versions. We are discussing holding a user group meeting on campus here at Hinxton, for early 2011, probably in January or February.

Please see the poll below....


We would also be interested to hear from one or two of our user-base to help plan and coordinate the event - if this sounds like you, please mail me.

P.S. We are also planning to hold another week long training course for ChEMBL resources next year, so keep an eye on the blog if you are interested in this.

Please note - the poll is now closed. We will try and arrange something in January or February next year, and would the people who were interested in helping us organise the meeting please make themselves known!

Thursday, 22 July 2010

EMBO Chemical Biology Meeting 2010


The 2010 EMBO Chemical Biology meeting to be held in Heidelberg is shaping up very well - excellent speakers, really exciting portfolio of international chemical biology research, etc, but it is now only two months away, however some places are still available for attendees. Links to the conference details are here.

Of course, several of the ChEMBL group will be there, and so if you'd like to meet any of us there, hear about our plans for the databases, or know more about research, drop us a line.

Monday, 19 July 2010

EMBL Postdoctoral Programme - Interdisciplinary Postdocs (EIPOD)


EMBL run an annual round of inderdisciplinary postdoc applications, with the research either from a set of pre-defined projects, or for projects of the applicants design. The positions reply on extensive collaboration between EMBL faculty, to produce an innovative and cutting-edge research opportunity. The deadline for applications to the EMBL EIPOD program is 5pm 31st August 2010. Details are at the following link, and we would welcome any applicants wishing to discuss potential projects with us.

Tuesday, 6 July 2010

Chembl_05 released

We are pleased to announce the immediate release of chembl_05, accessible through the front-end (at www.ebi.ac.uk/chembldb) and also available on the anonymous ftp server (ftp://ftp.ebi.ac.uk/pub/databases/chembl/). This release contains 7,493 targets, 697,730 compound records, 578,715 distinct compounds, 2,787,240 bioactivities abstracted from 36,624 publications. This correpsonds to a growth of 3% in bioassay count compared to chembl_04.

Monday, 5 July 2010

2010 New Drug Approvals - part IX - Sipuleucel-T (Provenge)

On April 29th, the FDA approved Sipuleucel-T (Tradename: Provenge, REsearch Code: APC-8015) a highly novel treatment (a cell-based vaccine) for hormone refractory (castration resistant) prostate cancer. Patients with this form of late-stage prostate cancer have refractory metastases after hormonal therapy even though they may have few symptoms. Sipuleucel-T has had a complex development and approval history (as a google search will readily show). Sipuleucel-T is a mixture of white blood cells that are extracted from the patient through a process called Leukapheresis, which is routinely used to isolate white blood cells e.g. for diagnostic purposes. In the 3 days that pass between the extraction of the white blood cells from the patient and the treatment with sipuleucel-T, the mixture is activated by exposing the extracted cells to an engineered protein called PAP-GM-CSF. In this, PAP stands for prostatic acid phosphatase (Uniprot P15309), which is produced in high amounts by metastasized prostate carcinoma cells. Among the cells extracted from the patient are antigen presenting cells which internalize the protein and, after lysosomal processing, present fragments of the proteins in conjunction with the immune stimulatory MHC class II molecules. This complex has an activating effect on all immune cells that have been in contact with PAP. Thus, upon re-infusion, the autologous immune cells promote a clonal growth of immune cells that are specifically active against the PAP-antigen and coordinate an immune response against the tumor cells, which present PAP antigen in abundance. In clinical trials with 512 patients, sipuleucel-T treatment increased patient survival by 4.1 months on average compared to no treatment. Among reported averse side effect are chills, nausea, fatigue and pain. Sipuleucel-T is marketed by Dendreon under the name Provenge. The full prescribing information for sipuleucel-T can be found here.

2010 New Drug Approvals - part VIII - Cabazitaxel (Jevtana)



ATC code (partial): L01CD

The FDA approved Cabazitaxel on June 17th. Cabitaxel is used in combination with prednisone to treat advanced, hormone-refractory prostate cancer.

Typically, prostate cancer occurs in older males and is among the most common forms of cancer affecting men with around 200,000 new cases per year diagnosed in the United States. Prostate cancer is a glandular cancer that is generally slow-growing. However, prostate cancer develops the ability to penetrate into other tissues and to form metastases.

Cabazitaxel is a new antineoplastic agent that inhibits the function of microtubules. Like other taxanes, it binds to beta-tubulin and promotes and maintains its incorporation in the assembled microtubule. As a consequence the dynamic structure of the microtubule cytoskeleton is 'frozen' and the concentration of free tubulin decreased. Mitotic cells, which depend on microtubules to restructure their shape and organelle organization, undergo apoptosis or stop progressing through the cell cycle. Thus, tumor growth is stalled.

Chemically, cabazitaxel is a dimethylated variant of the state-of-the-art treatment docetaxel. Cabazitaxel is an example of a semin-synthetic natural product, with the key raw ingredient isolated from yew leaves. Cabazitaxel is a lipophillic molecule with a high molecular weight 835.93 g.mol-1).
The volume of distribution (Vss) is 4,864 L. In vitro, the binding of cabazitaxel to human serum proteins was 89 to 92%. Cabazitaxel is mainly bound to human serum albumin (82%) and lipoproteins (88% for HDL, 70% for LDL, and 56% for VLDL). Cabazitaxel is extensively metabolized in the liver (> 95%), mainly by the CYP3A4/5 isoenzyme, and to a lower extent by CYP2C8. Clearance (primarily as metabolites) is via both urine and feces. Cabazitaxel has a plasma clearance of 48.5 L.hr-1.
Clinical trials with showed a statistically significant increase in survival rate by 2.4 month.
Cabazitaxel is to be administered as an intravenous infusion of 25mg/mm2(body surface) every three weeks in combination with a daily regiment of 10mg prednisone.
Cabazitaxel comes with a black box warning (fatal neutropenia). Patients have to be monitored for changes in neutrophil counts and treatment appropriately adjusted if a drop below 1500 neutrophils/mm3 is observed. Other adverse side effects of cabazitaxel are hypersensivity reactions, gastrointestinal symptoms and renal failure.

Cabazitaxel is marketed by Sanofi-Aventis under the name Jevtana. This is a link to the full prescribing information.




SMILES:
CO[C@H]1C[C@H]2OC[C@@]2(OC(C)=O)[C@H]3[C@H](OC(=O)c4ccccc4)[C@]5(O)C
[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)c6ccccc6)C(=C([C@@H](OC)C
(=O)[C@]13C)C5(C)C)C


InChI:
1S/C45H57NO14/c1-24-28(57-39(51)33(48)32(26-17-13-11-14-18-26)46-40
(52)60-41(3,4)5)22-45(53)37(58-38(50)27-19-15-12-16-20-27)35-43(8,
36(49)34(55-10)31(24)42(45,6)7)29(54-9)21-30-44(35,23-56-30)59-25(2)
47/h11-20,28-30,32-35,37,48,53H,21-23H2,1-10H3,(H,46,52)/t28-,29-,30+,
32-,33+,34+,35-,37-,43+,44-,45+/m0/s1

InChI-Key:
BMQGVNUXMIRLCK-OAGWZNDDSA-N
    

Chemdraw: cabazitaxel.cdx