ChEMBL Resources


Monday, 31 October 2011

Meeting: Drug Discovery Oxford 2012 - Drug discovery: a job too complex for academia or industry alone?

There is a great meeting being held in Oxford just after the Christmas break (specifically on the 5th and 6th January 2012), it's organised by the Structural Genomics Consortium, one of the longest existing advocates of Open Science in Drug Discovery.

Details of the meeting are here.

Friday, 28 October 2011

Thursday, 27 October 2011

The Bioinformoustachians!

The EBI has a team entered for the annual Movember fund raising event - this is focussed on raising money for 'male cancers' - testicular and prostate. The team is called The Bioinformoustachians!, so please consider sponsoring us over the coming month. Of course, as well as raising money for a serious cause, there will be some fun along the way as well. Watch over the next few days, as the full team signs up - we're gonna raise Loadsamoney (hopefully).

For those unfamiliar with the idea - participants are clean shaved at the start and grow a moustache throughout the month gaining sponsorship for looking stylish/silly.

The team webpage on the movember website is here. Please consider donating, and help us, together, make a difference.

New Drug Approvals 2011 - Pt. XXVIII Clobazam (OnfiTM)

ATC Code: N05BA09
Wikipedia: Clobazam

On October 24th, the FDA approved Clobazam (Tradename: OnfiTM; Research Code: RU-4723), a GABAA receptor agonist, for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged two years or older.

Lenox-Gastaut syndrome is a rare and severe form of epilepsy that is typically diagnosed in childhood and often persists into adulthood. LGS accounts for 1-4% of childhood epilepsies, and it is associated with multiple types of seizures, as well as, daily periods of frequent seizures.

Clobazam decreases the frequency of the LGS seizures by potentiating GABAergic neurotransmission, trough the binding of the GABAA receptor at the benzodiazepine site.

GABAA receptor is a protein complex of five subunits (mainly α2β2γ) located in the synapses of neurons. All GABAA receptors contain an ion channel that conducts chloride ions across neuronal cell membranes and two binding sites for the neurotransmitter GABA, while a subset of GABAA receptor complexes also contain a single binding site for benzodiazepines, also referred to as benzodiazepine receptors (BzR). Benzodiazepines, like clobazam, bind at the interface of the α and γ subunits on the GABAA receptor. Once bound to the benzodiazepine receptor, the benzodiazepine ligand locks the benzodiazepine receptor into a conformation in which it has a greater affinity for the GABA neurotransmitter. This increases the frequency of the opening of the associated chloride ion channel and hyperpolarizes the membrane of the associated neuron. The inhibitory effect of the available GABA is potentiated, leading to sedatory and anxiolytic effects.

Clobazam (IUPAC: 7-chloro-1-methyl-5-phenyl-1,5-benzodiazepine-2,4-dione; SMILES: CN1C(=O)CC(=O)N(c2ccccc2)c3cc(Cl)ccc13; PubChem: 2789; Chemspider: 2687; ChEMBLID: CHEMBL70418; Standard InChI Key: CXOXHMZGEKVPMT-UHFFFAOYSA-N) has a molecular weight of 300.7 Da, two hydrogen bond acceptors, no hydrogen bond donors, and has an ALogP of 2.74. Clobazam is a benzodiazepine derivative, a large and well established class of pharmacologically active compounds. So far, it is the only marketed 1,5-benzodiazenpine, being prefered over the 1,4-benzodiazepines already in the market: clonazepam and nitrazepam.

Clobazam is available as oral tablets of 5, 10 and 20mg, and the recommend daily dose is twice the amount of the tablets according to body weight. It has an apparent volume of distribution of 100L at steady state, and its relative bioavailability compared to an oral solution is 100%. The major metabolite of Clobazam is N-desmethylclobazam, which has about 1/5 of the activity of clobazam. Both compounds bind to human plasma proteins (80-90% and 70% respectively). The estimated mean elimination half-life (t1/2) is approximately 36-42 hr for clobazam and 71-82 hr for the active metabolite.

Clobazam is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C19 and CYP2B6. In vitro metabolism studies demonstrate that clobazam and its active metabolite induce CYP3A4 activity in a concentration-dependent manner. N-desmethylclobazam is extensively metabolised by the polymorphic CYP2C19, therefore, dosage in patients who are known CYP2C19 poor metabolisers may need to be adjusted. For further drug-drug interactions please refer to the full prescribing information.

Clobazam has been granted an orphan drug designation because it is intended to treat a condition that affects fewer than 200,000 people.

The license holder for OnfiTM is Lundbeck, and the full prescribing information can be found here.

Although clobazam has just been approved in the United States, it has been marketed outside of the US for several years under various brand names, including Frisium® and Urbanyl®, both licensed by Sanofi-Aventis. A full list of brand names can be found here.

Wednesday, 26 October 2011

New Drug Approvals 2011 - Pt. XXVII Deferiprone (FerriproxTM)

ATC code V03AC02 
Wikipedia Deferiprone

On October 14th, 2011 FDA announced the approval of Deferiprone (trade name: FerriproxTM) for the treatment of iron overload which is potentially fatal in patients with thalassemia. Deferiprone is an oral iron chelating agent, binding excess iron in the blood and thus making it available to excretion from the body. Thalassaemia is a inherited (mostly autosomal recessive) blood disease that can lead to anemia by causing the formation of abnormal hemoglobin molecules not able to properly bind and release oxygen. Thalassaemia (OMIM: 141800 (α-) / 141900 (β-)) is sub-classified according to which of the subunits of the hetero-tetrameric (2α/2β, UniProt: P69905 / P68871) hemoglobin is affected, contrary to sickle-cell anaemia (OMIM: 603903) which results exclusively from a specific mutation in the β subunit. The primary treatment of thalassaemia major, the severe form of β-thalassaemia, requires frequent blood transfusions to establish stable levels of functional hemoglobin but results in high levels of iron accumulating and impairing organ function. Thus, the secondary treatment aims on reducing the toxic iron levels by binding excess iron utilizing an iron chelating agent such as Deferoxamine (ChEMBL ID: CHEMBL556) requiring parenteral administration; Deferiprone has the desirable property of being orally available.

Deferiprone (3-hydroxy-1,2-dimethylpyridin-4(1H)-one, canonical SMILES: CN1C=CC(=O)C(=C1C)O, Standard InChI: InChI=1S/C7H9NO2/c1-5-7(10)6(9)3-4-8(5)2/h3-4,10H,1-2H3 , ChEMBL ID: CHEMBL556, CAS number: 30652-11-0, PubChem: CID 2972, ChemSpider: 2866) is a very simple synthetic small molecule with molecular weight of 139.152 Da, it has no rotatable bonds, two hydrogen bond acceptors, one hydrogen bond donor, ALogP of -0.14 and is thus fully rule-of-five compliant. 

Ferriprox is dosed as 500 mg tablets and administred orally three times daily in doses of 25 mg/kg to 33 mg/kg body weight (rounded to the nearest half-tablet), resulting in a daily molar dose of ~38-50 mmol for a 70 kg individual. Common adverse reactions include chromaturia, nausea, vomiting and abdominal pain, among others. Ferriprox is not suitable for pregnant or nursing women. Ferriprox reaches a maximum concentration (Cmax) of 20 mcg/mL, has an elimination half life (t1/2) of 1.9 hours and is excreted renally. The volume of distribution is 1.6 L/kg and 1 L/kg in thalassaemia patients and healthy subjects, respectively. Peak serum concentrations are reached 2 to 4 hours after administration.

Ferriprox has been issued a boxed warning for its potential to cause agranulocytosis/neutropenia, hematological disorders characterized by abnormally low numbers of white blood cells potentially leading to serious infections and death. 

Ferriprox is marketed and has been developed by Apotex

The full prescribing information can be found here. Prior to its approval in North America, Ferriprox has been approved and available in Europe and Asia for several years - approval in North America had been delayed considerably by safety concerns brought forward by a clinical researcher formerly involved in the clinical studies.

Tuesday, 25 October 2011

Recruitment - Two positions in ChEMBL team now available

We have two posts available in the ChEMBL group - one a web developer, and the other a data integration post. The positions are both for three years and will be EMBL staff contracts. Closing dates for applications is the 27th November 2011.

Further details should be available here (the links are quite fragile I'm afraid, so sorry if they do not keep working for long)

If you have any questions, please feel free to contact us.

Monday, 24 October 2011

PhD studentship at the Institute of Cancer Research

From the lab of one of our collaborators comes the following......

Details of forthcoming PhD studentships at The Institute of Cancer Research ICR are now on-line; There are 12 studentships across a range of different disciplines including Biology, Chemistry, Informatics and Medical Physics. The deadline for applications is 1st December 2011.

There is a specific studentship of likely interest to ChEMBL-og readers - Identifying novel targets and target combinations for cancer using in-silico chemical biology, within the Computational Biology and Chemogenomics Team of the ICR.

This is a computational biology/lab biology PhD jointly between Dr. Bissan Al-Lazikani and Prof. Paul Workman. The project is an exciting multi-disciplnary project that will utilise bioinformatics and chemogenomics techniques, protein interaction network modelling as well as laboratory biology to identify novel drug intervention targets (and compounds) for use in combination therapies with best-in-class HSP90 inhibitors. The first two years of the project will be primarily computational (with an opportunity to do some basic Mass. Spec. proteomics work in the laboratory) and focus on multi-omics data mining, network modelling chemogenomic and druggability analysis. Discoveries made though the first two years will then be validated in the laboratory utilising RNA interference, cellular drug screening and other molecular and cellular biology techniques. The project benefits for a collaboration with Dr. Paul Huang and Dr. Julio Saez-Rodriguez (of the EMBL-EBI) who bring network proteomics and network modelling expertise.

Full details of the project can be found here.

The PhD is a four year project funded through the MRC studentship program. Please check eligibility criteria before applying.

Want to help shape the future of ChEMBL?

We are planning to hold two half-day (fun) workshops in mid February next year (i.e. the week of February 13th 2012). Aimed at medicinal chemists and molecular modellers - the idea is to develop easy to use workflows for several key tasks that drug discoverers often want to do, and could do more efficiently with the ChEMBL data.

The workshops will be on campus here at Hinxton, and will start around 10.30am and finish around 3pm (lunch, coffee and cakes will be provided); the focus will be on....

  • Day 1 - Use of ChEMBL in lead optimisation
  • Day 2 - Use of ChEMBL for library design/compound purchase

If you are interested in helping, please mail us, and tell us what session you'd most like to attend. Space will be limited to around 8 attendees.

Friday, 21 October 2011

Why Movember is Important

'Excluding skin cancer, prostate cancer is the most commonly diagnosed cancer among men in the US and the second most common cause of cancer death among men. It is estimated that about 1 in 6 men in the US will be diagnosed with prostate cancer during their lifetime and 1 in 36 will die from this disease.'

Quote from Cancer Facts & Figures 2010. American Cancer Society

Paper: canSAR

One of our collaborators has just published a paper in NAR Database issue on an integrative system for Anticancer Drug Discovery - canSAR.

%J Nucleic Acids Research
%D 2011
%O doi:10.1093/nar/gkr881
%T canSAR: an integrated cancer public translational research and drug discovery resource
%A M.D. Halling-Brown
%A K.C. Bulusu
%A M. Patel 
%A J.E. Tym
%A B. Al-Lazikani
The website for canSAR is

Wednesday, 19 October 2011

Some Downtime is Coming Up....

Our Hinxton Data centre is being shutdown this coming weekend (Saturday 22nd and Sunday 23rd October 2011) for some essential maintenance. Most of the ChEMBL services will still run through this period from our London Data Centers.

The key exception to this is the Structure-based Druggability Service and Portal (

Further details of the shutdown can be found here.

Tuesday, 11 October 2011

UKQSAR and ChemoInformatics Group Autumn 2011

The UKQSAR and ChemoInformatics Group Autumn 2011 Meeting, jointly hosted by Accelrys and Astex, will be held on Thursday November 3rd at the Accelrys European Headquarters in Cambridge.

Details of the one day meeting can be found here. Looks a great meeting.

Wednesday, 5 October 2011

Are You Ready For Movember?

We are.

EMBL and Russian Foundation for Basic Research call for Proposals

On 1 October 2011, EMBL and the Russian Foundation for Basic Research (RFBR) issued a call for joint projects. The 2012 call for financial support for a basic research project covers the following priority areas:
  • Structural biology
  • Genomics
  • Biomolecular chemistry
  • Cell biology/imaging
  • Technology development XFEL life science
  • High-performance computing
Biomolecular Chemistry will include Chemical Biology, Cheminformatics, Chemogenomics, QSAR, Predictive Toxicology, Virtual Screening, etc. The supported research must be carried out jointly by Russian and EMBL scientists and be of mutual interest. The call is open until 30 November 2011. If any Russian Federation scientists are interested in working with ChEMBL on an application for this funding call, please get in touch.