The ChEMBL-og

On Friday July 10th we plan to hold a further Druggability Workshop for the EMBL-EBI Industry Partners. If anyone is interested in participating in this highly interactive and participatory workshop AND also interested in joining the Industry Partner program; please contact me.....

Third on our series of posts on new FDA drug approvals this year is Golimumab, approved on the 24th of April. Golimumab is a tumor necrosis factor alpha (TNFα) blocker indicated for the treatment of active forms of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Golimumab is the fourth TNF inhibitor, after Etanercept, Infliximab and Adalimumab, to reach the market. Etanercept is a fusion protein of an engineered from the the TNF receptor fused to IgG1, while Infliximab and Adalimumab are very similar to Golimumab structurally in that they are all 'conventional' monoclonal antibodies. Golimumab (previously known as CNTO-148) is a human monoclonal antibody that exhibits multiple glycoforms with molecular weights of ca. 151 kDa. Golimumab has a good subcutaneous (sc) absorption ( ca. 53% bioavailable), a plasma half-life of ca. 2 weeks, a volume of distribution of 58 to 126 mL/kg and a systemic clearance of 4.9 to 6.7 mL/day/kg. The recommended dosage of ...

Second onto market this year is Febuxostat, approved on the 13th of February. Febuxostat is a xanthine oxidase inhibitor used for the treatment of hyperuricemia (gout), and competes against well established agents such as Allopurinol (Allopurinol was approved in 1964 for the treatment of gout). Febuxostat is a small molecule drug (Molecular Weight of 316.4 g.mol-1) is fully Rule-Of-Five compliant, is essentially insoluble in water, and has good oral absorption (>49% bioavailable). Febuxostat plasma half-life of 5 to 8 hours, a volume of distribution of 50L, high plasma protein binding at 99.2% (unsurprising given the lipophilic acid nature of the molecule). Febuxostat is extensively metabolised, both by the UGT system, producing glucoronidated metabolites, and also by a range of complex CYP mediated transformations (metabolites of metabolites....). Some of the CYP mediated metabolites involve hydroxylation of the butyl sidechain, these themselves are pharmacologically active again...

An occasional series of posts with news and top level details on new FDA drug approvals. The series is a little retrospective at the moment, but it will not take much time to catch up for 2009. First 'out of the gates' on 14th Jan this year is an 'old' compound, Milnacipran (Savella in the US) for the treatment of fibromyalgia syndrome . Milnacipran is an SNRI (Serotonin Norepinephrine Reuptake Inhibitor, and as such blocks the function of the norepinephrine transporter NET and the serotonin transporter SERT ), like all compounds of this pharmacological class, the molecule is small (Molecular Weight of 246.4 g.mol -1 for Milnacipran itself, and 282.2 g.mol -1 for the HCl salt) is fully Rule-Of-Five compliant, has high aqueous solubility, and also has good oral absorption (85% bioavailable) and metabolism characteristics. (A plasma half-life of ca. 8 hours, a volume of distribution of 400L, low plasma protein binding at 13%. Excretion is renal (through the kidneys a...

Here is a link for a Royal Society of Chemistry (RSC) meeting held in Stevenage in October. The schedule is.... 10.00 Herbert Waldmann MPI of Molecular Physiology, Dortmund, Germany Bioactivity Guided Navigation of Chemical Space 10.40 John Overington European Bioinformatics Institute, Hinxton, UK ChEMBL - Open Access Databases and Tools for Drug Discovery 11.20 Malcolm Young University of Newcastle, UK Counterintuitive properties of complex networks in brains and cells 12.00 Lunch 13.00 Chris Schofield University of Oxford, UK The Hypoxic Response - from Molecules to Systems 13:40 Albert Heck University of Utrecht, The Netherlands Chemical Proteomics: Exploring the Role of Small Molecules in Molecular Systems Biology 14.40 Seth Grant MRC Cambridge, UK Synapse Systems Biology: New Models of Brain Organisation 15.20 Glenn Prestwich University of Utah, Salt Lake City, USA Engineered Extracellular Matrices for Drug Discovery and Reparative Medicine 16.00 Round Tab...

The Society for Medicines Research ( SMR ) is a UK-based society for those interested in drug research, they hold a regular series of meetings themed around particular areas. When I got home yesterday, in my letterbox,I found the flyer for their next meeting, which looks good, so I thought I would post details here, and potentially encourage people to either go, or maybe even join the SMR. The next meeting focussing on site-specific delivery of particular therapeutic agents and principles of local drug delivery is on the 11th June and is at Horsham in West Sussex. The program and registration form can be found here . The picture above I found on the web , It is of a 'letterbox' letterbox, sort of recursive, eh?

Now that is one cool tattoo! Hey, "StARlite" has eight letters too, that gives me a good idea for a prize in a future competition.... The next StARlite schema walkthrough will be held on Friday 8th May, at 11am BST. It will last about 45 minutes, and require dialling a UK phone number for audio. We now have a reliable web desktop sharing system (we have settled on the wonderful Open Source webhuddle , also on SourceForge ) and a reliable conference phone system, so there should be no technical issues ;), this time. If you wish to take part, please click this link for further details....

It is a public holiday in the UK today (we call these bank holidays , for reasons that seem obscure nowadays). The weather is traditionally bad on such days, and today is no exception, at least the remainder of the week, when we return to work, will be fine and sunny. We will run a further StARlite schema and query walkthrough webinar shortly, but in the meantime here are some skeleton sql queries, that perform a set of related queries retrieving compounds/bioactivities for a given target. In this case the target is human PDE4A (for which the tid is 3), and human PDE5A (for which the tid is 276). We will walk through getting these unique target identifiers (or tids) on another occasion, but suffice it to say, that this is easy, especially programmatically, using blastp. Firstly, retrieving a set of potent inhibitors of human PDE4A or PDE5A. There are a number of parameters one needs to set to actually do this (the end-point, the affinity cutoff, etc. Specifically here we have sel...