ChEMBL Resources

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

Saturday, 30 January 2010

FAQ: How do I get some advice on how to use chembl?

The simplest way is to contact us at chembl-help@ebi.ac.uk.

FAQ: I've done some virtual screening using chembl, can you send me the compounds?

We do not have physical samples of any of the compounds in chembl, so we cannot supply any samples to you. Sorry. If you want to obtain samples of chembl compounds you do have a number of options: 1) Often the underlying literature contains a synthetic route and reagents for the compounds, this greatly helps resynthesis. 2) About 5-10% of chembl compounds are reported to be available from compound vendors (for example, you could search databases such as the excellent ZINC to find available compounds). However, the turnover of stock from compound vendors is quite high, and often a significant fraction of compounds reported to be available for purchase will be out of stock when you want them.

Tuesday, 26 January 2010

2010 New Drug Approvals - Pt. II - Dalfampridine (Ampyra)


The second NME approval this year is Dalfampridine (trade name Ampyra), approved on January 22nd. Dalfampridine is a potassium channel blocker indicated to improve walking in adults with multiple sclerosis. Multiple sclerosis is a serious chronic disease that affects the central nervous system and in which the myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring. The therapeutic mechanism of Dalfampridine is complex, has not been fully elucidated, but it has been shown to increase conduction of action potentials in demyelinated axons through inhibition of potassium channels, probably Shaker channels.

Dalfampridine is a (very) small molecule drug (Molecular Weight 94.1 g.mol-1), fully Rule-of-Five compliant and soluble in water. Dalfampridine (also known as 4-AP) has good oral bioavailability (96% bioavailable), with a volume of distribution of 2.6 L/kg and low plasma protein binding. Excretion is mainly renal (95.9% of the dose recovered in urine) and mostly as the parent drug (90.3%). Dalfampridine metabolites are 3-hydroxy-4-aminopyridine and 3-hydroxy-4-aminopyridine sulfate (a sulphated form of the previous metabolite). These metabolites have no pharmacological activity on potassium channels. The elimination half-life of Dalfampridine is 5.2-6.5 hours. The maximum recommended dosage is 10mg twice daily (equivalent to a dose of 106uM) and full prescribing information can be found here. Dalfampridine chemical structure is 4-aminopyridine, a very simple unremarkable structure.

NAME="Dalfampridine" TRADEMARK_NAME="Ampyra"
SMILES="n1ccc(N)cc1"
InChI="InChI=1/C5H6N2/c6-5-1-3-7-4-2-5/h1-4H,(H2,6,7)"
InChIKey="NUKYPUAOHBNCPY-UHFFFAOYAH"
ChemDraw=Dalfampridine.cdx

The license holder is Acorda Therapeutics, Inc. and the product website is www.ampyra.com.

Papers for Abstraction into Chembl...



We would be keen to hear of key SAR publications that people would like entered into chembl (if they aren't there already). Send us the PubMed id, and we'll add it to our list, and then see whether it is in scope (and budget!) of chembldb.

If we get sufficient input of this, we'll post the list of papers.

Sunday, 24 January 2010

SMR Meeting: Regenerative Medicine, Cambridge 11th March 2010


The SMR run arguably the best series of UK-based drug discovery meetings - they're cheap, they are on one day and they attract great speakers, and they are pharma/biotech focussed. The next is
Regenerative Medicine: A New Frontier for Therapeutic Intervention
to be held on the 11th of March, at Granta Park in Great Abington, just outside of Cambridge. Further details are on the SMR website

Tuesday, 19 January 2010

Anyone in the Bay Area interested in a Chembl seminar in March 2010?


We are speaking at the Spring ACS National meeting in San Francisco (in the polypharmacology section - it will almost exclusively be new slides!). This is in the week of March 21st to 25th 2010.

If there is any interest in a seminar, database demo, or just a chat and (fine) coffee/(so-so) beer, it would be good to meet up, so mail me if you'd like to meet.

Monday, 18 January 2010

Chembl_02 - Press Release



This morning, there was a press release released, marking the official release of chembl_02. More details are in the press release, but for the blog audience, the data is available in the interface, and the databases available for download on the ftp site. Work is already underway on chembl_03, with some associated minor changes to parts of the schema and additional curation of data. There is also something exciting and special in chembl_03, but more of that later.

There is approximately 20% more data in chembl_02 than chembl_01 and new content highlights include a significant expansion of Natural Product records, and unification of all compound identifiers across all EMBL-EBI records (we use ChEBI ids) all chembldb compounds should now seemlessly and quickly make their way into PubChem.

Many, many thanks to those who have told us of the errors and ambiguities you have found. We will incorporate all of these back into the database for the entire community.
For newer readers a pointer, and for older readers with poor memory, a reminder, of the chembl FAQ, and keep an eye open of the chembl-og (or even better the RSS feed) for schema walkthroughs, support and so forth.

Two pieces of staffing news for the group. Firstly, congratulations to Patricia for her success in getting selected for an EIPOD - this is for a joint collaborative project in peptide SAR between the Koehn and Overington groups. Secondly, we welcome our first PhD student - Felix Krueger, who is immersing himself in programming, databases, British life, and data.

Complementary to the required formality of the press release - some thanks! The entire Chembl team would like to take this opportunity to thank our many friends and colleagues who have helped to date, and will do so in the future. In particular, the Wellcome Trust (especially Alan and Rebecca) for their vision and funding (and Janet, Chris, Henning and Bissan for their essential roles in the grant), the senior management of EMBL, especially Iain and Janet, for their wisdom and continuous support. We'd like to acknowledge the assistance our growing network of external curators (Malcolm, Sam, Lora, and Karen), previous interns (good luck Jigisha!), and outsourcing partners (especially Jignesh and the team). Bissan and Mark at the ICR were essential in the early days of the group, and achieved so much while we were recruiting, and they remain an important part of our work and plans. We also thank and recognise the management and staff of Inpharmatica and their investors, for much of the initial development of the databases was done at that time - you know who you are!. Prof. Hopkins, as ever, you are a star ;) Most essential though has been the friendship, focus and shared purpose of our new colleagues at the EMBL-EBI - especially our new friends in the ChEBI team, as well as the INTACT, Systems, Outreach, PANDA, HSF, EBI Industry programme partners, and many other new friends and colleagues, both at Hinxton and Heidelberg. Finally, finally; we have also been doubly blessed with 1) being able to continue working with several long-term collaborators, and 2) finding new important ones since starting at the EMBL-EBI. The future looks bright, so thank you all!

Sunday, 17 January 2010

New Drug Approvals - Pt. XXIV - Bepotastine Besilate (Bepreve)

We're mopping up a few drug approvals from 2009 we have not yet covered yet as monographs... Approved on September 8th 2009 was Bepotastine Besilate, marketed under the trade name Bepreve. Bepotastine is a topical, selective and non-sedating histamine (H1) receptor antagonist indicated in the treatment of itching associated with allergic conjunctivitis. Through the H1 binding, Bepotastine has broad range of anti-inflammatory effects - a stabilizing effect on mast cells, inhibition of eosinophil migration and interleukin-5 (IL-5), leukotriene B4 (LTB4) and platelet activating factor (PAF) release. Bepotastine has been previously approved in Japan, under the trade name Talion, for allergic rhinitis (2000) and urticaria and skin pruritus (2002). Bepotastine is a chirally pure, synthetic small molecule drug (Molecular Weight 388.89 g.mol-1 for Bepotastine itself and 547.06 g.mol-1 for the dosed besilate salt), is Rule-of-Five compliant and is delivered as an ophthalmic solution. Bepotastine has a low protein binding of approximately 55%, is minimally metabolized by CYP450 isozymes and elimination is mainly through renal excretion (approximately 75-90% excreted unchanged in urine). The recommended dosage is one drop directly to the infected eye(s) twice a day. The prescribing information can be found here. The structure (+)-4-[[(S)-p-chloro-alpha-2-pyridylbenzyl]oxy]-1-piperidine butyric acid, with no unusual reactive features. There is a single stereocenter in the structure, and Bepotastine is dosed as the (+) enantiomer. The physicochemistry will be dominated by the Zwitterionic nature of the molecule - a molecule of nett neutral charge, but which contains compensatory charge centers - in this case the basic nitrogen of the central piperidine ring, and the carboxylic acid (on the far right of the compound figure).
NAME="Bepotastine"
DRUG_TARGET="MSLPNSSCLLEDKMCEGNKTTMASPQLMPLVVVLSTICLVTVGLNLLVLYAVRSERKLHT
VGNLYIVSLSVADLIVGAVVMPMNILYLLMSKWSLGRPLCLFWLSMDYVASTASIFSVFI
LCIDRYRSVQQPLRYLKYRTKTRASATILGAWFLSFLWVIPILGWNHFMQQTSVRREDKC
ETDFYDVTWFKVMTAIINFYLPTLLMLWFYAKIYKAVRQHCQHRELINRSLPSFSEIKLR
PENPKGDAKKPGKESPWEVLKRKPKDAGGGSVLKSPSQTPKEMKSPVVFSQEDDREVDKL
YCFPLDIVHMQAAAEGSSRDYVAVNRSHGQLKTDEQGLNTHGASEISEDQMLGDSQSFSR
TDSDTTTETAPGKGKLRSGSNTGLDYIKFTWKRLRSHSRQYVSGLHMNRERKAAKQLGFI
MAAFILCWIPYFIFFMVIAFCKNCCNEHLHMFTIWLGYINSTLNPLIYPLCNENFKKTFK
RILHIRS"
SMILES="Clc1ccc(cc1)C(OC2CCN(CCCC(=O)O)CC2)c3ncccc3"
InChI="InChI=1S/C21H25ClN2O3/c22-17-8-6-16(7-9-17)21(19-4-1-2-12-23-19)27-18-
10-14-24(15-11-18)13-3-5-20(25)26/h1-2,4,6-9,12,18,21H,3,5,10-11,
13-15H2,(H,25,26)"
InChIKey="YWGDOWXRIALTES-UHFFFAOYSA-N"
ChemDraw=http://www.ebi.ac.uk/chembl/downloads/Bepotastine.cdx
Bepreve is marketed by IstaVision and the product website is here

Wednesday, 6 January 2010

Links to/from chembldb


If there are any cool or neat things that anyone has done with the chembldb data and is available on the web (either with an interface or as a web service) we are very happy to link to this from our pages. So if you have anything you want linked, let us know.

Monday, 4 January 2010

Chembldb schema walkthrough - 3pm GMT, 15th January 2010


We will host another web-meeting walkthrough of the chembldb core database schema on Friday 15th January at 3pm GMT. If you are interested in joining, please email us on this link for dial-in details. We will be using the webhuddle software for the demo so it may be worth trying it out on your machine beforehand.

Sunday, 3 January 2010

Species in Chembldb


Thanks to Richard Bickerton at the University of Dundee here is a nice rendering of the species/genus/phyla of the targets in chembldb. Click the image to get a larger, readable view.