The ChEMBL-og

On June 21st 2011, the FDA approved azficel-T (trade name:  laViv ) for the aesthetic treatment of moderate to severe nasolabial fold wrinkles in adults ("smile lines"). laViv is an autologous cell therapeutic , consisting of fibroblasts (cells which can produce  collagen ) which are produced from a biopsy of post- auricular tissue by proliferation in vitro , and re-injected into the nasolabial folds to improve their cosmetic appearance. With increasing age, nasolabial folds can become more pronounced, caused by habitual facial expressions ( i.e. laughing ), and a decline of collagen production. Alternative non-drug treatments include liposuction and facelift . After biopsy, dermal fibroblasts are expanded using standard tissue-culture procedures until a sufficient amount of cells for re-injection is obtained. This process takes 11-22 weeks. laViv is provided in two vials of approximately 18 million fibroblasts in 1.2 mL suspension and should be administere...

To study proteins in the context of a cellular system, it is essential that the molecules with which a protein interacts are identified and the functional consequence of each interaction is understood. A plethora of resources now exist to capture molecular interaction data from the many laboratories generating such information, but whereas such databases are rich in information, the sheer number and variability of such databases constitutes a substantial challenge in both data access and quality assessment to the researchers interested in a specific biological domain. The paper is available here , and here is the PSICQUIC registry . %T PSICQUIC and PSISCORE: accessing and scoring molecular interactions %A B. Aranda %A H. Blankenburg %A S. Kerrien %A F.S.L. Brinkman %A A. Ceol %A E. Chautard %A J.M. Dana %A J. De Las Rivas %A M. Dumousseau %A E. Galeota %A A. Gaulton %A J. Goll %A R.E.W. Hancock %A R. Isserlin %A R.C. Jimenez %A J. Kerssemakers %A J. Khadake %A ...

ATC code: L04AA28 On June 15th 2011, the FDA has approved Belatacept (trade name: Nulojix ; Research Code: BMS-224818), a selective T-cell (lymphocyte) costimulation blocker indicated for phophylaxis of organ rejection in adult patients receiving a kidney transplant. Belatacept is approved for use in combination with other immunosuppressants , specifically basiliximab, mycophenolate mofetil and corticosteroids. Belatacept is a potent antagonist that inhibits T-lymphocyte activation by binding to the B7-ligands , namely CD80 (Uniprot: P33681 ; Pfam: PF08205 , PF07686 ) and CD86 (Uniprot: P42081 ; Pfam: PF07686 ), present on antigen-presenting cells, and thereby blocking interaction with CD28 (Uniprot: P10747 ; Pfam: PF07686 ), the receptor of these two ligands. This interaction provides a costimulary signal necessary for full activation of T-lymphocytes. Activated T-cells are the predominant mediators of immunologic rejection. In vitro , Belatacept inhibits T-cell prolif...

ATC code:   N03 AX21 On June 10th, FDA approved ezogabine (trade name Potiga , NDA 022345 ) to treat seizures associated with epilepsy in adults. However, before being launched, Potiga waits categorised by the Drug Enforcement Agency (for  review under the  Controlled Substances Act ) before formal marketing can proceed. Epilepsy is a chronic neurological disorder involving a variety of symptoms caused by abnormal electrical activity in the brain. Episodic bouts ('seizures') can potentially be controlled by medication - however, for around 1 in 3 patients, this can not achieved satisfactorily  with current medication.  Ezogabine (ChEMBLID: 41355 ) represents a novel approach, being the first anticonvulsant to specifically target neuronal potassium channels .  The molecular targets of ezogabine are KCNQ/Kv7 potassium channels; by stabilizing their open conformation , the drug reduces their excitability. It shares its mode ...

We are starting to plan a few things, and one of these is to provide links through to the sources of physically available compounds for ChEMBL. To help us, here's a few questions - I tried to set up an online poll, but lost the will to live with all the spam on polls that is out there. Here are the questions: Is integration of available compounds in ChEMBL a good idea? Should we integrate available compounds via current informatics resources ( e.g . ZINC , ChemSpider )? Should we set up a small set of available compounds from actual suppliers ( e.g . NCGC , MolPort , Prestwick , ChemDiv , Tocris , etc . etc .). If so what suppliers should we use? If you want to contribute,  free to mail if you have any specific ideas, or can help us out on this.

Not Moon Safari but Kinase SARfari ! There are a lot of changes to the interface and integration of data, and also oodles more data (104% more) contained in the latest release. These include: Unified SARREGNOs to CHEMBL IDs (also Assay & Doc ids). Updated assays, activities and compounds from ChEMBL_10. Added 30 non-human kinase domains. Calculated site similarity distances and neighbourhood density (ND) scores between all kinase domains. Added Drug Icons into the interface. Added links to ChEMBL Target/Doc/Assay Report Cards. Renamed old sources (drugstore & candistore). Contents: Kinase domains: 989, Kinase bioactivity datapoints: 435,873, Kinase compounds: 51,090. For the time being, the new version can be found on our dev site at http://wwwdev.ebi.ac.uk/chembl/sarfari/kinasesarfari . As always, we would appreciate any bug reports, feedback, etc .

There are two group leader positions currently listed at the recruitment pages for the Heidelberg site for EMBL. Due to the goofy web recruitment system we have, I can't give a link to the jobs themselves, but you should be able to find them from here . Areas of interest for one of these posts include: structural bioinformatics ( e.g. modeling of protein complexes and their interactions and/or dynamics in a cellular context). image analysis/visualization ( e.g . reading out data from GFP screens, E-tomograms or visualizing a virtual cell atlas). cheminformatics (e.g. chemical-protein-network analysis). systems bioinformatics ( e.g. tissue modeling, analysis network perturbations). transcriptional regulation/epigenetics ( e.g . chromatin modification analysis). The closing deadline is June 19th 2011 - so real soon!!

We are involved in a fascinating collaboration with   Prof. Aroon Hingorani   from the Clinical Epidemiology Dept of UCL Division of Medicine - working with clinical data (phenotype and GWAS) to identify new approaches to the treatment of cardiovascular disease (drug reuse, patient stratifcation, etc .). Further details of the position are   here . Closing date is June  24th 2011. Cool passport eh?

There is an interesting course being run in Oeiras , Portugal in July. About one hundred million different chemical compounds have already been synthesized. The number of theoretically possible organic molecules exceeds the number of atoms in the universe. This raises a number of questions, including: Where can one find information about chemical structures and their properties? How can one efficiently retrieve such information? Which molecules, if synthesized, could potentially assist the fight against certain types of cancer? Why is it that some pharmacological targets are considered more promising for the prevention or treatment of Alzheimer?s disease than others? Are there ways to better predict ADME(T) properties of synthesized molecules? Why does such a significant proportion of launched drugs originate from structures found in natural products? Why can multi-target pharmacological agents be superior to single-targeted o...

We are pleased to announce the release of ChEMBL_10. This latest version of the ChEMBL database contains: 1,118,566 compound records 1,000,468 distinct compounds 534,391 assays 4,668,202 bioactivities 8,372 targets 40,624 documents 6 data sources This release of the ChEMBL database contains a subset of the data from the PubChem BioAssay database. Specifically, we have included dose-response endpoints ( e.g. , IC 50 , Ki, Potency) from confirmatory assays in PubChem - the aim of this is to integrate data that is comparable to the type and class of data contained within ChEMBL. This subset contains: 333,864 compound records (PubChem Substance entries) 794 assays (PubChem BioAssay assays) 1,473,189 bioactivities (IC 50 etc. measurements) You can access the data via the ChEMBL database interface: http://www.ebi.ac.uk/chembldb/index.php . Changes to the interface include: 'Activity Source Filter' link has been added to the main search bar to allow users to in...

For those of you who use the safari browser  as part of your normal work, Matt Swain has written a plugin that you might find useful. You simply highlight words within a page, right-click, and then a box pops up with the option to search chembl for that chemical structure (using the selected text as the query). Matt also wrote similar plugins for C hemSpider , PubChem and OPSIN . These, and more, are available here . Thanks Matt!

Well, so are we! If you are interested in applying for a postdoctoral fellowship in our group we would welcome you contacting us for further details. The position would apply text mining approaches across the broad internet to 'discover' interesting disclosures of either compound structures, progression through key clinical development or regulatory milestones, evidence of therapeutic efficacy for a compound/mechanism class etc . This data would be placed into the public domain, and integrated against other data sources, including ChEMBL , clinicaltrials.gov and other relevant data sources. You will need to have prior experience of entity recognition within free text, great scripting skills in a language such as perl or python, web analytics, and internet search engines (but hey, who doesn't know how to use google ?). Additionally, experience of chemical structure extraction (image and/or text-based), ontology use/building and data integration and mining skills would be g...

ATC code (partial): A07A On May 27th 2011, the FDA approved Fidaxomicin (Tradename: Dificid ; Research Code: PAR-101, OPT-80, NDA 201699), a macrolide narrow spectrum antibacterial drug indicated for the treatment of Clostridium difficile -associated diarrhea (CDAD) in adults. Clostridium difficile ( C. difficile ) is an anaerobic, spore-forming Gram-positive bacteria , and overgrowth of this species can cause severe diarrhea and other more serious intestinal conditions, such as colitis . Fidaxomicin is a fermentation product obtained from the Actinomycete Dactylosporangium aurantiacum . It exerts its therapeutic effect by inhibiting beta subunit of the bacterial enzyme DNA-directed RNA polymerase (RNAP) (UniProt: Q890N5 ), resulting in the death of C. diffi cile . Bacterial RNA polymerase is a large (~400 kDa) five subunit protein, and is the target of the already approved antibiotic rifampicin . Other treatments for CDAD already in the market include anti...