The ChEMBL-og

Yesterday, Cancer Research UK press released the launch of the first full version of canSAR - the Institute of Cancer Research's integrated cancer research and drug discovery resource. canSAR integrates large volumes of disparate data covering most aspects of cancer biology and chemistry, and is an example of how to complement the chEMBL database with therapeutic area specific knowledge. canSAR integrates biological annotation, gene expression, RNA interference studies, structural biology and protein interaction network data - as well as chemical and pharmacological data. It contains annotation on the entire human proteome, and contains >8 million experimental data points including RNAi and chemical screening data. For full release notes please see canSAR news . canSAR is updated monthly. As well as the wonderful chEMBL, the data in canSAR comes from a large number of sources, including ArrayExpress , PDBe , ROCK , STRING , Genomics of Drug Sensitivity in Cancer , COSM...

I am doing a surprising amount of molecular graphics stuff at the moment, and have finally realised I don't have the skills or coordination to use a mouse/keyboard to do simple rotations/scaling/clipping etc. So, it turns out it's possible to connect up a dial box to a aMacBook Pro, with a little bit of messing around with drivers. So does anyone have an old, unwanted dial box for an SGI machine? Part numbers  9980991,  9980992, and  9780804 are all apparently OK. If you have one of these, let me know .

ATC code (partial): H01AC Also this month, on November 10th, FDA has approved Tesamorelin under the trade name Egrifta. Tesamorelin (research code:TH-9507) is an analog of the human growth hormone-releasing factor (GRF)  (UniProt: P01286 , synonym:Somatoliberin, synonym:GRF, synonym:GHRH) indicated for the reduction of excess abdominal fat in HIV -infected patients with lipodystrophy . Lipodystrophy is a condition in which excess fat develops in atypical areas of the body, most notably around the liver, stomach, and other abdominal organs. This condition is observed as a side effect with many antiretroviral drugs used to treat HIV. Tesamorelin is the first-FDA approved treatment specifically approved for lipodystropy. The -relin INN stem covers prehormones or hormone releasing peptides, a very broad range of targets and pharmacology. The -morelin stem sub-group covers growth hormone-release stimulating peptides including capromorelin, dumorelin, examorelin, ipamorelin, pralm...

One big problem of simple sequence searching with tools like blast  with ChEMBL is the problem of the introduction of contextually incorrect target relationships due to matching of irrelevant domains. For example, imagine a protein, X , that contains two domains of types A and B , and a second protein, Y , which contains also two domain types, B and C . If the ligand is known to bind to domain type A , there is no ligand-binding relationship between X and Y ; however, if the ligand binds at domain type B in X , then there is a relevant relationship between X and Y . This may sound like an rare example, but it is surprisingly common (and extremely annoying), since the majority of eukaryotic proteins are multi-domain, and the presence of certain domains, such as an EGF-like domain (Pfam: pf00009 ) can greatly complicate the analysis of sequence searches. What is really needed is a reliable mapping (or more generally a probabilistic score) of the ligand-binding domains within a p...

The ChEMBL Database User Group on Linkedin is perilously close to 100 members - in fact we need just one more to make it to the magic century! We have found a well known industry figure to help organise our first User Group meeting, and we'll start posting details shortly on the LinkedIn group site.

Here is a call for assistance, all input will end up published on The ChEMBL-og , and accessible to one-and-all. What we're looking for is a pretty comprehensive list of key clinical candidate disclosure meetings, ideally those with disclosure of chemical structure, functional assay, pharmacokinetic and toxicology data - you know the sort of meeting, where the key data on a hot compound is disclosed for the first time. I've put together a preliminary list here , from memory and a little bit of googling - this is far, far, far from perfect and is woefully incomplete, and am now looking for addition of extra meetings for the areas not covered, and some highlighting of additional ones. As you will see I've used the ATC classification for the structure of the list - although this is not perfect for things like anti-microbials, etc., it is actually a pretty good framework to hang this off. If you have any suggestions, please mail them in .... Finally, if you are intereste...

ATC code (partial): L01C On November 15th, 2010, the FDA approved Eribulin Mesylate (ResearchCode:E-7389) under the trade name Halaven (TradeMark: Halaven ). It is indicated for for the treatment of patients with late stage, metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Phase III trials showed that patients survived a median of 2.5 months longer than patients treated with other current alternatives. Eribuln is a synthethic analogue of halichondrin B , a cytotoxic polyether macrolide marine natural product. The mechanism of action of Eribulin is anti-mitotic and is mediated via tubulin binding, where it leads to G2/M block in the the cell-cycle ; after prolonged stalling in this state, cells enter apoptosis and are then cleared. Eribulin is a large (Mwt 729.9 for Eribulin and 826.0 for the mesylate salt) synthetic compound (an analogue of halichondrin B) an IUPAC name of the s...

We are pleased to announce the release of chembl_08. This version of the ChEMBL database was prepared 26th October 2010 and contains: 735393 compound records 636269 compounds (of which 635933 have molfiles) 488898 assays 2973034 activities 8088 targets 38462 publications 5 activity data sources You can also download the ChEMBL database (Oracle 9i, 10g, 11g or MySQL) from our ftp site: ftp://ftp.ebi.ac.uk/pub/databases/chembl/ChEMBLdb/latest/ . Changes to the database (please see release notes for more detail): FDA approved drugs have now been added to the compounds table*. Some drugs (e.g., biotherapeutics) do not have a structure/molfile, and not all drugs have bioactivity data associated with them. Further information for these drugs (e.g., mechanism of action) will be added in subsequent releases. Parent compounds have been generated by removing the salt component from any compounds tested as a salt form. Both the parents and the salt forms are recorded in the compounds ...

The next Society for Medicines Research meeting is on the 9th December 2010 at the National Heart and Lung Institute , Kensington, London. These are my favourite day meetings, cheap, well organised and very applied to actual drug discovery. This meeting there are some great talks. Unfortunately, I cannot go to the SMR meeting - I will be ill (probably), in a hotel (hopefully), maybe on the beach (certainly) at the Zing Structural Biology Conference.  The graph above answered an important question for me.

ATC code (partial): J01DI On October 29th, FDA has approved Ceftaroline Fosamil under the trade name Teflaro. Ceftaroline Fosamil (previously known by the research code TAK-599, the parent drug, Ceftaroline is also known as T-91,825) is an antibiotic indicated for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive and Gram-negative microorganisms, such as Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes , Streptococcus agalactiae , Escherichia coli , Klebsiella pneumoniae , and Klebsiella oxytoca , and also for the treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible Gram-positive and Gram-negative bacteria, such as Streptococcus pneumoniae (including cases with concurrent bacteremia ), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae , Klebsiella pneumoniae , Klebsiella oxytoca , an...

Registration for the 2011 residential ChEMBL Training course, running from the 14th to the 18th of Feburary, is now underway, further details can be found at this link . What better way to spend Valentine's Day ? The picture above is of the ingredients in a Twinkie , apparently.

The EBI recruitment website now has the EU-OPENSCREEN developer position detailed. Closing date is the 12th December 2010 . The job is an exciting opportunity to work on establishing a pan European archive of academic screening data.

ATC code (partial): N05AE On October 28th 2010, the FDA approved Lurasidone (Tradename:Latuda) (Lurasidone is also known by the research code SM-13,496). Lurasidone is an atypical antipsychotic agent indicated for the treatment schizophrenia. Lurasidone displays broad polypharmacology against a wide range of rhodopsin-like aminergic GPCRs, acting as an antagonist with high affinity at dopamine D2 receptors (Uniprot: P14416 , ChEMBL: 72 ) (Ki of 1 nM), serotonin 5-HT2A (Uniprot: P28223 , ChEMBL: 107 ) (Ki of 0.47 nM) and 5-HT7 receptors (Uniprot: P34969 , ChEMBL: 10209 ) (Ki of 0.49 nM), and with moderate affinity at alpha-2C adrenergic receptors (Uniprot: P18825 , ChEMBL: 218 ) (Ki of 10.8 nM) and at alpha-2A adrenergic receptors (Uniprot: P08913 , ChEMBL: 52 ) (Ki of 40.7 nM). Lurasidone acts also as a partial agonist at serotonin 5-HT1A receptors (Uniprot: P08908 , ChEMBL: 51 ) (Ki of 6.4 nM) and exhibits little or no affinity for histamine H1 (Uniprot: P35367 , ChEMBL: 127 ) ...

Some of the ChEMBL team are in Tokyo, Japan for the week of 14th to 18th March 2011. We are there for some training with a valued collaborator. We have some spaces in our schedule so we could visit and talk if there is interest. We have a native Japanese speaker in our group, and so we can present in both Japanese and English. If you would like us to visit you please mail . ChEMBLチームは、2011年3月14日の週に、日本の東京を訪問します。日本にいる素晴らしい協力者と直接お会いし、トレーニングコースを行う予定です。今のところ、まだスケジュールに余裕がありますので、ChEMBLにご興味がある方々をいくつか訪問したいと思っています。ChEMBLチームには、日本人メンバーがいますので、日本語と英語の両方でプレゼンテーションを行うことができます。ご興味がありましたら、是非こちらまでメール( kaz@ebi.ac.uk )をお送りください。よろしくお願いいたします。

ATC Code: B01AE07 Dabigatran etexilate has been approved by the FDA on October 19th 2010. Dabigatran etexilate (also known as BIBR-1048 for Dabigatran etexilate and BIBR-953 for Dabigatran) is approved for the treatment of patients with atrial fibrillation at risk of embolism or stroke. Dabigatran etexilate is a first-in-class (for the US) oral drug preventing blood clotting and stroke by direct inhibition of thrombin and is marketed under the trade name Pradaxa in Europe and the US, and Pradax in certain other territories. In Europe, an earlier oral direct thrombin inhibitor Xemelagatran  (trademark:Exanta trademark:Exarta also known as H376/95) was approved, but subsequently was withdrawn due to commercial and perceived safety issues. The formation of blood clots in the circulation can cause embolism or stroke (or CVA) if other risk factors are present.  Depending on the number of risk factors, the risk of suffering a stroke increases up to 7-fold in patients with atr...