ChEMBL Resources

The SARfaris: GPCR, Kinase, ADME

Sunday, 27 February 2011

New Drug Approvals 2011 - Pt. IV Human coagulation Factor XIII Concentrate (CorifactTM)

ATC code : B02BD07

On February 17th 2011, the FDA approved human coagulation Factor XIII (FXIII) Concentrate as an orphan drug under the trade name Corifact (ATC code B02BD07) to treat congenital Factor XIII deficiency (OMIM:134570 and OMIM:134580, ICD-10:D68.2). The incidence of this rare condition is 1 in 1 to 5 million, making it the rarest form of hemophilia. The genetic deficiency leads to defective fibrin crosslinking, the terminal step of the coagulation cascade which leads to blood forming clots to deplete its loss from damaged vessels.

Prior to US approval, FXIII Concentrate had already been marketed in Europe, as Fibrogammin P,  developed by CSL Behring of Marburg, Germany. Recently, recombinant FXIII (rFXIII, Novo Nordisk, Bagsv√¶rd, Denmark) has completed phase 3 clinical trials.

FXIII exists naturally as a secreted, tetrameric protein (with composition A2B2) with a molecular weight of ca. 320 kDa. The tetramer consists of twice two catalytically active transglutaminase (A subunit, Uniprot:P00488) (E.C. and an enzymatically inactive carrier (B subunit, Uniprot:P05160) subunits in the blood plasma, or as a catalytically active dimer (A2) inside platelets, monocytes, macrophages and their respective precursor cells. The B-chain holds the A chain dimer in an inactive state, and also shields the A-chain from proteolytic degradation in the plasma.

>Corifact A chain
>Corifact B chain

Several crystal structures are available for the catalytically active A chain dimer of FXIII, e.g. PDBe:1EVU.

FXIII is activated by proteolytic cleavage of the first 37 N-terminal amino acids by thrombin (also known as factor II). In presence of calcium ions, the carrier subunits dissociate, leading to a conformational change exposing the catalytic center of the A chain, thus capable of crosslinking of fibrin molecules to form an insoluble clot. In order to restore natural coagulaton, patients suffering from FXIII deficiency can therefore be treated with exogenous FXIII.

The half-life (t1/2) of Corifact is 6.6 days, with a steady state Volume of distribution (Vss) of 52, and a Clearance (Cl) of 0.25

Corifact is made from pooled human donor blood plasma, and is supplied as lyophilized concentrate for intravenous administration after reconstitution with sterile water. The recommended initial dosing is specific to the patients body weight and existing blood coagaultion parameters. Typical dosage is 40 IU per kg body weight and is repeated every 28 days. In the subsequent dosing, FXIII activity levels are monitored, and adjusted to achieve the intended trough FXIII activity level. As a human blood product, the production process of Corifact is monitored to minimize possible contamination with virus (e.g., HIV, HAV, HBV, and HCV), and the infective agent of CJD.

The full prescribing information can be found here.

The license holder for Corifact is CSL Behring, and the product website is here.

Saturday, 26 February 2011

ChEMBL web pages in Chinese

Thanks to Yumi for the translation of our ChEMBL home page into Chinese. At the moment, this is on the dev site, but it will soon migrate to the normal location.

Tuesday, 22 February 2011

ChEMBL_09 BioTorrents Available

The flat files (sdf, chemical representatives, fasta and release notes) and the mysql dump from the latest ChEMBL release are now available as torrents on the BioTorrents website, click here for more details. We have been a bit slack in maintaining the ChEMBL BioTorrent downloads, but will always aim to make the these torrent files available for future ChEMBL releases.

Friday, 11 February 2011

Chembl_09 Schema - A Different View

The guys at the NCI Cactus blog have done a great job of rendering the new ChEMBL schema as released in ChEMBL_09. There are quite a few changes, and we have started to load/curate new data against this schema - so check with us if your analyses rely on something currently in there! Click on the above image for a large view.

Things will be fairly quiet at ChEMBL Manor next week - we have the annual ChEMBL training course which will keep us busy, and hopefully out of any trouble.

Thursday, 10 February 2011

EMBL-EBI Open Day March 2011

Registration is now open for the next EMBL-European Bioinformatics Institute Open Day, which will take place on Tuesday 15th March 2011.

The 'Open Day' is the perfect opportunity for young scientists who are considering a career in bioinformatics (and related disciplines) to find out more about opportunities at Europe's main centre for bioinformatics. You will learn about cutting-edge research projects, get an overview of one of the world's most important collections of biological databases and tools, and be given time to talk one-to-one with the experts who develop and curate these services. There is also the chance to hear a talk from one of the ChEMBL team, talking about a curator job.

Registration is FREE, but places are limited to 40 so please register now to avoid disappointment. Please go to for a full programme and registration details.

Monday, 7 February 2011

ChEMBL_09 released

We are pleased to announce the release of ChEMBL_09 and a new version of the ChEMBL web interface. This release of the ChEMBL database contains initial entries for small molecule and biotherapeutic drugs, together with product information from the FDA Orange Book. This data will be subject to further updates and curation in subsequent releases and therefore some property assignments should be considered preliminary. It should also be noted that a number of the approved products do not have therapeutic uses (e.g., diagnostic agents, additives etc.). These non-therapeutics are currently included in the database, but are flagged as such. We have also now incorporated the chemical structures of ligands from entries in PDBe (Protein Data Bank in Europe) into to ChEMBL.

Use of ChEBI IDs: ChEMBL will continue to assign ChEBI identifiers to small molecules with known structures, and these compounds will be indexed by ChEBI for search purposes. However, only a subset of highly curated entries will be displayed on the ChEBI web-interface or provided in their downloads. ChEMBL compounds are also now deposited directly into PubChem.

Schema Changes: There are significant schema changes this release, to allow the incorporation of the approved drug data. Please see release notes for more details.

  Interface Enhancements:
  1. 'Browse Drugs' tab, which allows users to view, search and download the drug data stored in ChEMBL database (
  2. A new Document report card page has been created, which summaries target, activity, compound and assay data found in a ChEMBL journal article. All previous links to PUBMED now go to this page (e.g.
  3. Only parent compound structures are returned in the compound searches
  4. Bioactivity results display both parent and salt/ingredient structures
  5. Compound report cards updated to include a Clinical Trials and Molecular Forms sections (e.g.
  6. A choose of 3 compound sketchers (JME, Marvin, JDraw) are now available on compound search page
  7. Japanese translation of home page

Sunday, 6 February 2011

Choice of chemical sketchers now available within ChEMBL

There are a lot of excellent chemical sketchers available, and we have now implemented a choice of three within the ChEMBL interface - JME Molecular Editor, Jdraw and MarvinSketch. These three were the three most requested chemical drawing packages, but if there is demand for more please feel free to suggest additional ones.

Please consider this multi-sketcher capability as still in a test phase, and please report any problems you find.

Saturday, 5 February 2011

ChEMBL web pages in Japanese

ChEMBL is now available in a Japanese language form (to access this, just click on the appropriate flag at the top right of the ChEMBL home page).

Tuesday, 1 February 2011

Conference: Joint Sino-UK Protein Symposium, Shanghai, May 5-7 2011

I have been invited to speak at the Biochemical Society and Chinese Protein Society Joint Sino-UK Protein Symposium being held on the 5th to 7th of May at Shanghai University, China. Some excellent speakers on the agenda, including David Stuart, David Barford, Guy Dodson, and Zhang Youshang. Immunizations and visa office here I come!