The ChEMBL-og

In the likely case one of your New Year resolutions was to use ChEMBL data more, here's a new paper introducing ChEMBLspace by some of our Eli Lilly collaborators. ChEMBLspace is a standalone Java application that enables users to visualise and explore an extensive network of human proteins. Two such proteins are connected if they have at least one ligand in common, as reported in the ChEMBL database (version 14). A user may select proteins and list their ligands interactively and then design an activity profile iteratively by adding more targets or anti-targets to the selection and adjusting protein-specific activity thresholds. The compounds that meet the desired profile are displayed within the application (with links to ChEMBL) and the full collection can be saved as an SD file. You will find the paper here while the source code and standalone jar file are here . You may even modify the code provided and so link the application to your ow...

The power and insight provided by structural biology into pharmacology can never be underestimated, and significant progress is now possible for previously challenging target systems for structure determination, most notably the GPCRs, which we regularly cover here on the ChEMBL-og. However, there are an increasing number of ion channel and transporter structures being determined. We are probably in sight of the time when the majority of pharmacology for known drugs can be placed in a three-dimensional structure setting. We live in exciting times! Here is a paper on a further important drug target family - the ligand-gated ion channels - more specifically structural studies on the multimeric ligand-binding extracellular domain. The work involved the engineering of a more tractable homolog ( Aplysia AChBP - Aplysia is a sea hare if you are interested) of the human 5HT3 receptor ( 5HT3R ) to become more 5HT3-like in it's ligand binding properties (Pfam: Neur_chan_LBD PF02931 ...

ATC code:  A16AX08 Wikipedia: Teduglutide On December 27, FDA approved Teduglutide (Tradename: Gattex®, Tradename: Revestive, Research Code: ALX-600, CAS# 197922-42-2), an analog of Glucagon-like peptide 2 ( GLP2 ) expressed in  Escherichia coli by recombinant DNA ( rDNA ) technology indicated for the treatment of adult patients with Short Bowel Syndrome ( SBS ). Short Bowel Syndrome (MeSH:  D012778 ) is a condition in which nutrients are not properly absorbed ( malabsorption disorder) caused by surgical removal of small intestine, or rarely due to the complete dysfunction of large segment of bowel. More information about SBS can be found in Medscape . Teduglutide is an analog of naturally occurring Glucagon-like peptide 2 (GLP2), which is 33 amino acid peptide created by specific post-translational proteolytic cleavage of proglucagon in endocrine L cells of the distal intestine. GLP2 is known to increase intestinal an...

ATC code: H01CB05 Wikipedia: Pasreotide On December 14, the FDA approved Pasireotide diaspartate (SIGNIFOR®, Research CodeL SOM-230, CAS#  396091-73-9 , Pub-Chem :  CID 9941444 , KEGG :  D10147 ), a cyclohexide with pharmacologic properties mimicking those of natural hormone Somatostatin for treatment of adult patients with Cushing's disease  (CD) for whom pituitary surgery is not an option or has not been curative. Cushing's disease (CD) is a cause of Cushing's syndrome characterised by increased secretion of ACTH (adrenocorticotropic hormone) from the anterior pituitary. CD is a rare hormone disorder, and  recent statistics indicate that the annual incidence is somewhere between 1 and 10 per million and is 3 times more common in women than in men (from NEMDIS ). This is most often as a result of pituitary adenoma  or due to excess production of hypothalamus Corticotropin releasing hormone ( CRH ). More information can be found i...

ATC code: not yet assigned Wikipedia: Crofelemer On December 31 2012, the FDA approved Crofelemer for the treatment of diarrhea caused by antiretroviral medication regimens taken by patients with HIV/AIDS . Diarrhea is a frequent adverse effect of antiretroviral medication - however, it can also be caused by secondary infections of the gastrointestinal tract or the virus itself. The loss of fluids incurred by diarrhea can lead to dehydration and electrolyte imbalance. As a side-effect of antiretroviral medication it also reduces patient compliance with a prescribed medication regimen. Crofelemer alleviates the symptoms of HIV-associated diarrhea by limiting the amount of chloride ions that are pumped into the intestinal lumen, thus also retaining sodium ions and water. Crofelemer is a natural product oligomer that is not orally bioavailable but acts locally on the intestinal surface. It was shown to inhibit two distinct intestinal chloride channels expressed in...

ATC code: not yet assigned Wikipedia: Cabozantinib On November 29th, the FDA approved  Cometriq TM (cabozantinib, research code XL-184) for the treatment of patients with progressive, metastatic, medullary thyroid cancer (MTC). MTC is a rare type of thyroid cancer accounting for 5-10% of all diagnosed thyroid cancers ( CRUK ). A quarter of MTC cases are familial and are caused by a mutation in the RET gene. Clinical studies showed that cabozantinib increases progression-free survival time to 11.2 months in comparison with 4 months for placebo. Cabozantinib (research codes: XL-184, BMS-907351; IUPAC:  Cabozantinib ( S )-malate is described chemically as N -(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)- N’ -(4-fluorophenyl)cyclopropane- 1,1-dicarboxamide, Standard InChI:  ONIQOQHATWINJY-UHFFFAOYSA-N) is dosed as the (S)-malate salt. The parent molecule, cabozantinib, has a molecular weight of 501.5 and a ACD/LogP of 3.08. The effective half-life is ~55 ho...

Happy New Year! We are making some necessary changes to the schema in the forthcoming ChEMBL 15. These will almost certainly break scripts, or lead to changes in search results if you have developed applications based on the previous ChEMBL schema. If you are likely to be affected by these changes please consider the following actions. Review the Release Notes for previous releases of ChEMBL, where these changes were outlined. Watch the ChEMBL-og for further announcements. We will run a webinar on the key elements of the schema change and the way it is likely to affect data integration. Sign up to the chembl-announce mailing list. Let us know that you do develop applications using ChEMBL, and we will try and consider any specific dependencies you may have. Consider the likely impact of the changes prior to scrubbing your previous install and cussing us when it doesn't work out-of-the-box ;) jpo