Saturday, 30 January 2010
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
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
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
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
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
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
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.cdxBepreve is marketed by IstaVision and the product website is here