ChEMBL Resources


Sunday, 21 February 2010

Beta-testing new version of kinase SARfari

A new data load for kinase SARfari screening data has just been completed. There is a significant growth in both the number of inhibitors (28,016 vs. 17,028), and the number of assay data-points (147,478 vs. 68,861).

It is available here

Remember it is a test version only, and if you do find any problems, please mail them...

Finally, there is a funny story behind the picture, which will emerge over the next few blog posts.

Monday, 15 February 2010

2009 New Drugs - Clarification on Dysport/AbobotulinumtoxinA

We have had a couple of mails about the exclusion of AbobotulinumtoxinA (aka Dysport) as a new NME in some of our analyses of drugs for 2009. This is a subtle case, and our treatment of AbobotulinumtoxinA is as follows - but basically it is not an NME.

Recently the FDA required that, due to the non-interchangeability, and potential safety issues of Botulinum Toxin A products from different manufacturers, that differing non-proprietary names were required for these products, despite the fact that nominally they contain the same active ingredient (in this case a large protein therapeutic). So Botox, marketed by Allergan, now uses the non-proprietary name onabotulinumtoxinA, while for Dysport (approved during 2009) from Ipsen, uses the non-proprietary name abobotulinumtoxinA. Since they essentially just differ by manufacturer, and not by active ingredient, we have not considered Abobotulinum toxin as being a new NME approval.

Saturday, 6 February 2010

Two New Posts within the ChEMBL Team

We have recently been awarded an Innovative Medicines Initiative grant in the area of predictive toxicology - the project is called eTox. This is a very exciting project and will build an unprecedented collaborative database of rat toxicology data for a large number of clinical development candidates. It is also a chance to work in close collaboration with a network of some of the leading European academics, SMEs and pharmaceutical companies.

We have two posts available under this funding. The first is for a scientist with experience of datamining and analysis of data, preferably with good experience of bioinformatics or chemoinformatics. The second post is for an informatician to build a data repository, and then populate this with deposited curated toxicology data.

If you have any questions about the jobs, please feel free to mail us.

The deadline for applications is 14th March 2010.

2010 New Drug Approvals - Pt. III - Liraglutide (Victoza)

ATC code: A10BX07

Also approved in January is Liraglutide, on January 25th, under the trade name Victoza. Liraglutide, previously known as NN2211, is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. People with this type of diabetes are often overweight, have high blood pressure and/or cholesterol and become insensitive to insulin. Type 2 diabetes is the commonest form of diabetes, and is a major health problem in 'developed' economies. Liraglutide ATC code is A10BX07

Liraglutide works by activating the GLP-1 receptor (GLP-1R), which in turn stimulates the adenylyl cyclase pathway leading to insulin release in the presence of elevated glucose concentrations. GLP-1R is a class-II GPCR (also known as secretin receptor family). Liraglutide is the second GLP-1 agonist approved for the treatment of type 2 diabetes, after Exenatide (marketed as Byetta), which reached the market in 2005. Other -glutides in development include Taspgolutide (R1583 or BIM-507) developed by Roche, and Abiglutide (a stabilized GLP-1 analogue fused to serum albumin) from GSK. Liraglutide is an engineered form of the natural human GLP-1 peptide (one amino acid difference to the major circulating form of GLP-1, GLP-1(7-37) - an arginine replaces a lysine at position 34), an additional modification is the addition of palmitic acid attached via a glutamic acid spacer at position 26. The molecular weight of Liraglutide is 3751.2 Da.

Each standard dose contains 1.8mg of Liraglutide (equivalent to 480 nmol). Dosing is as a once daily subcutaneous (s.c.) injection. Liraglutide has a plasma half-life of ~13 hr (far longer than the ca. 2 min half life of the natural GLP-1 peptide). Slowing the fast degradation of GLP-1 is the basis of the therapeutic mechanism of the -gliptin class of DPP-IV inhibitors, e.g. Saxagliptin and Sitagliptin). The absolute bioavailability of Liraglutide, after s.c. dosing is 55%, and has high plasma protein binding > 98%. The volume of distribution Vd is 0.07L/kg, with a clearance of 1.2 L/h. Liraglutide has a boxed warning (risk of thyroid C-cell tumours). Victoza is marketed by Novo Nordisk and the product website is

2010 New Drug Approvals - Pt. I - Tocilizumab (Actemra/RoActemra)

The first FDA approval of this year is Tocilizumab, approved on January 8th, under the trade name Actemra. Tocilizumab is a first-in-class interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody drug, and is indicated for the treatment of rheumatoid arthritis in adults who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Rheumatoid arthritis is a chronic and debilitating, systematic inflammatory disorder, which affects principally synovial tissues. Tocilizumab ATC code is L04AC07. Tocilizumab works by blocking the signalling of IL-6, an immune system soluble cytokine that is overproduced in patients with rheumatoid arthritis. Other biological therapies for RA include tumor necrosis factor-α (TNF-α) blockers (e.g, Golimumab), IL-1 blockers (e.g., Anakinra), monoclonal antibodies against B cells (e.g., Rituximab) and T cell costimulation inhibitors (e.g., Abatacept). However, all these act through binding to different target molecules. Others drugs with the same IL-6R binding mechanism as Tocilizumab are ALD518 and CNTO-136, which are currently reported to be in Phase II clinical trials. Tocilizumab is a recombinant humanized anti-human IL-6 receptor monoclonal antibody of the immunoglobulin IgG1κ subclass. Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R) - mIL-6R is also known as CD126. Tocilizumab has a molecular weight of ca. 148 kDa, with a volume of distribution of ~6.4L, a linear clearance of ~12.5 mL/h and a half-life up to 13 days. The recommended starting dosage is ~4 mg/kg followed by an increase to ~8 mg/kg based on clinical response, administrated as a single intravenous drip infusion over 1 hour, every 4 weeks. Interestingly, Tocilizumab, via blocking cytokine signalling can affect expression levels of a wide variety of CYP450 drug metabolizing enzymes, leading to the potential for drug-drug interactions. The full prescribing information for Tocilizumab can be found here. Tocilizumab has a boxed warning (Risk of serious infections). Each light and heavy chain of Tocilizumab consists of 214 and 448 amino acids, respectively, and the four polypeptide chains are linked intra- and inter-molecularly by disulfide bonds. The license holder of Tocilizumab is Genentech, Inc. and the product website is

Tuesday, 2 February 2010

Minor revisions to Chembl interface

Many thanks to the attendees on the Small Molecule Bioactivity Course at the EMBL-EBI last week. We have a big list of things to fix, a bigger list of things to think about, and despite thinking three weeks ago that we would never want to do the course again, are now looking forward to it again next year.

We have made some minor interface changes, available at

Frr those of you waiting for the interface/database webinars, something will be announced soon...