ChEMBL Resources

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

Friday, 30 October 2009

Kinase SARfari Update

The Kinase SARfari interface has been updated and is now using the JME Molecular Editor for compound drawing and editing. JME is an easy to use fast loading applet, for more information visit: http://www.molinspiration.com/jme/

ChEMBL notifications, updates, social media and news.


When I started work, if you wanted to tell someone something, you wrote a handwritten note, posted it internally to a typing pool, told them how many copies you wanted, and a few days later things would turn up in the internal post. To distribute things further, you had to then fill envelopes, lick stamps and then post them. (For the youth reading this, Google any of the unfamiliar words/phrases). It was incredible that anything got done at all (penicillin, the transistor, gps, etc it really is.
We live in different times, and as a group we communicate in three general ways to the world.

  • The ChEMBL-og chembl.blogspot.com - this blog! Mostly news of broad interest, some ephemera, some recruitment, and some analyses of data, new drug approval news, interesting papers, conferences, book and hotel reviews for scientists, etc.
  • The Group homepage at www.ebi.ac.uk/chembl - links to the online resources (currently kinase sarfari and chembldb are live).
  • The ChEMBL twitter feed www.twitter.com/chembl - mirrors most posts from the blog, occasional 'just had a really tasty burger', 'need a quarter inch Whitworth spanner', you have been warned.
  • The chembl-announce mailing list listserver.ebi.ac.uk/mailman/listinfo/chembl-announce - formal news about data/software releases.

    The picture above is from b3ta (Often NSFW) - the United Kingdom have a major (physical) postal strike in the UK at the moment.

Wednesday, 28 October 2009

Chembl database web interface and data downloads are now live


The initial web front-end to the ChEMBL SAR data is now available on the EMBL-EBI website, as are data downloads in MySQL and a variety of Oracle format downloads.

The web interface is at http://www.ebi.ac.uk/chembldb/index.php

The database downloads are at ftp://ftp.ebi.ac.uk/pub/databases/chembl/chembl_01/

We'll add some front-end documentation in the near future, and also restart the schema walkthrough web meetings, so if you are interested in these, please sign up to the chembl-announce mailing list, or configure an RSS feed on the blog.

The picture above is the unbelievable 'King of Herrings', a charmingly named and only occasionally encountered deep sea oarfish, it is the world's longest bony fish you know...

Recruitment: Data Integration for ChEMBL


We have a new position available within the ChEMBL group from January 2010 onwards - the role is for someone to do data integration, analysis, and work-flow prototyping for chemogenomics/bioassay data. The post should be advertised on the EMBL recruitment website soon, there are also several other excellent jobs listed at EMBL-EBI.

Conference: TACBAC 2010


Registration for TACBAC 2010 is now open - TACBAC stands for Therapeutic Applications of Computational Biology and Chemistry. Details on the conference can be found here

Deadline for Bursaries for Small Molecule Bioactivity Course is Approaching




The deadline for application for bursaries for the small molecule bioactivity course at the EMBL-EBI is approaching - Friday November 6th. If you wish to attend for free (or at a really discounted rate) please consider applying now. We are starting to assemble the material for the course now, and have secured some truly outstanding external speakers - it should be good!

Sunday, 25 October 2009

SMR Award Meeting: Recent Disclosures of Clinical Candidates - December 10th, London.


There is, what looks like, an excellent meeting in London, full details are on the SMR website. I hope I feel better by then.


SMR Award Meeting: Recent Disclosures of Clinical Candidates
10th December 2009
 
National Heart & Lung Institute, Kensington, London
Programme:

09.30
Registration and coffee
10.00
SMR Award lecture: The Discovery and development of Januvia, Dr. Ann Weber, Merck
(Introduction by - Rob Williams, 
Cancer Research UK)

Session 1 - Chair: Mark Searcy, University of East Anglia
11.00   
Chris Murray, Astex
From fragment to clinic - the discovery of the hsp90 inhibitor, AT13387.
11.45
George Muller, Celgene
The discovery of apremilast.
12.30
Lunch (Including SMR AGM 13.10-13.30)
Session 2 - Chair: Diane Coe, GSK
13.30
David Fox, Pfizer
The discovery of a second generation long-acting PDE5 inhibitor.

14.15
Simon Hodgson, GSK
The discovery of a dual H1/H3 antagonist for allergic rhinitis.

15.00
Tea
Session 3 - Chair: David Fox, Pfizer
15.30
Karl Gibson, Pfizer
The discovery of a progesterone receptor antagonist for endometriosis.
16.15
Mairi Gibson, GSK
Second generation EP1 antagonists for the treatment of pain.
17.00
Close

Wednesday, 14 October 2009

ChEMBL interface: Call for Testers

So, we have an initial interface for the ChEMBL SAR data, and we are looking for some interested people to do some testing, find issues with different OS, browsers, java versions, etc. The kinase SARfari testing we did was very helpful, and many, many thanks to those of you that helped, but rest assured, we will mail you for feedback, bugs, etc.

If you wish to take part, please mail us

Kinase SARfari has been updated

We have released an update to Kinase Sarfari, the major changes are:

Frontend Changes

  1. Compound report card now displays smiles, inchi, inchi_key
  2. Bioactivity data download now includes smiles
  3. User guide updated
  4. Starlite references changed to ChEMBL

Backend Changes

  1. Migrated kinasesarfari schema from chemdev to chempro (an internal trifle, but important to us ;)
  2. Schema clean up

Thanks for all the feedback!

Thursday, 1 October 2009

New Drug Approvals - Pt. XIX - Pralatrexate (Folotyn)



Also approved on September 25th was Pralatrexate (tradename Folotyn). Pralatrexate is the first drug approved for the treatment of Peripheral T-Cell Lymphoma (PTCL), an aggressive form of non-Hodgkins lymphoma. Lymphoma is a cancer that begins in the lymphocytes of the immune system. PTCL is a rare disease, occurring in around 9,500 patients each year in the United States.
Pralatrexate, also known as PDX, is a folic analog that competitively inhibits dihydrofolate reductase (DHFR). Since Pralatrexate blocks the use/function of a metabolite, it is also an antimetabolite. Pralatraxate has high affinity for the folate transporter SLC19A1 (also known as RFC-1), and so is an example of a drug that is 'actively transported', and is also a substrate for polyglutamation by the enzyme folylpolyglutamate synthase (FPGS). Once polyglutamated Pralatrexate has a prolonged intracellular half-life, giving prolonged action in malignant cells. Pralatrexate is related to several other drugs, most notably Methotrexate, and 'old' launched drug, and also the clinical stage compounds - Ketotrexate, Edatrexate, and also the antiprotozoal agent Trimetrexate, all of which are DHFR inhibitors.
Pralatrexate is a polar, racemic small molecule (Molecular Weight of 477.5 g.mol-1), soluble in aqueous solutions. Pralatrexate is a mixture of diastereomers (stereoisomers that are not enantiomers, i.e. they are non-superimposable). Diastereomers can have different physical properties biological activities, and different reactivity. Pralatrexate has a volume of distribution (Vd) of 105L and 37L for the S- and R-diastereomers, respectively, a plasma protein binding (ppb) of 67%, a systemic clearance of 417 mL.min-1 (S-diastereomer) and 191 mL.min-1 (R-diastereomer), and an elimination half-life (T1/2)of 12-18 hours. Pralatrexate is not significantly metabolized by the phase I hepatic CYP450 isozymes or phase II hepatic glucuronidases, and has low potential to induce or inhibit the activity of CYP450 isozymes - elimination is primarily of unchanged drug in urine.
The recommended dosing of Pralatrexate is 30 mg.m-2 administrated as an intravenous injection once weekly for 6 weeks in 7-week cycles. The full prescribing information can be found here.

The structure (2S)-2-[[4-[(1RS)-1-[(2, 4-diaminopteridin-6-yl)methyl]but-3-ynyl]benzoyl]amino]pentanedioic acid is a folate analog in which the hydroxyl group of the pyrimidine ring has been replaced by an amine, and the central amino group of the molecule has been replaced by a stereocenter carbon with a methylacethylene attached to it (which may undergo nucleophilic atack). Pralatrexate diastereomers differ in configuration at this stereocenter only, and so they are also epimers.
<CHEMBL_DRUG>
<DRUG_NAME="Pralatrexate" TRADEMARK_NAME="Folotyn" APPROVAL_DATE="25-SEPT-2009" DRUG_MOLECULAR_WEIGHT=477.5>
<DRUG_STRUCTURE>
<DRUG_SMILES="O=C(O)[C@@H](NC(=O)c1ccc(cc1)C(CC#C)Cc2nc3c(nc2)nc(nc3N)N)CCC(=O)​O">
<InChI="InChI=1/C23H23N7O5/c1-2-3-14(10-15-11-26-20-18
(27-15)19(24)29-23( ​25)30-20)12-4-6-13(7-5-12)21(33)28-16
(22(34)35)8-9-17(31)32/h1,4-​ 7,11,14,16H,3,8-10H2,(H,28,33)(H,31,32)(H,34,35)(H4,24,25,26,29,3​ 0)/t14?,16-/m0/s1">
<InChIKey="OGSBUKJUDHAQEA-WMCAAGNKSA-N">
</DRUG_STRUCTURE>
<ChemDraw="Pralatrexate.cdx">
<DRUG_TARGET>
VGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKTWFSI
PEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSSV
YKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFE
VYEKND
</DRUG_TARGET>
</CHEMBL_DRUG>
The license holder is Allos Therapeutics, Inc. and the product website is www.folotyn.com.