The ChEMBL-og

ATC Code: A08A (incomplete) Wikipedia: Lorcaserin On June 27 th , the FDA approved Lorcaserin hydrochloride (Tradename: Belviq TM ; Research Code: APD-356), a selective serotonin 2C receptor  (5HT2c) agonist, for chronic weight management in adults with an initial body mass index ( BMI ) equal or higher than 30 kg/m 2 (obese), or equal or higher than 27 kg/m 2 (overweight) and with one weight-associated comorbid condition (e.g. hypertension , dyslipidemia , type 2 diabetes ). Lorcaserin is believed to decrease food consumption and promote satiety by selectively activating 5-HT 2C receptors on anorexigenic pro-opiomelanocortin neurones in the hypothalamus. The exact mechanism of action is not fully established. However, at therapeutic concentrations, lorcaserin is selective for 5-HT 2C receptors as compared to 5-HT 2B receptors, making it less prone to cardiovascular side-effects, associated with previous 5-HT 2C  weight management drugs. It is the f...

So some very sad news yesterday - the announcement of the closure of the Nutley R&D facilities of Roche . Families disrupted, kids moved to new schools, partners careers affected, and then inevitable greater competition for the few remaining jobs and downward pressure on salary and benefits. It's a tough time to be a drug discoverer wanting to work in industry. Quite striking to me in this is the geographical focussing of the drug discovery industry in three places, Cambridge MA, Cambridge Cambs (or 'Cambridge Classic' as I call it) and Basel (you could also add a fourth, South San Francisco to this list, maybe). You can understand why this happens, the companies want access to a 'liquid' talent pool, and employees want 'robustness' to future layoffs, and this leads to focussing of 'resources' in a few geographical locations. Would be interesting to pull together the data for the last 40 years on R&D site locations and staff sizes, and ...

This is a last call for people who would like to sign up for the "Schema & SQL Querying" webinar that will be hosted this Wednesday 27th June at 3.30pm (BST). It will be a 45 minute webinar that will take you through the ChEMBL schema and also how to use SQL queries to extract data from the database. Remember to register your interest in our webinars on the   Doodle Poll . Make sure that you leave your **email address** as well as your name so that we can send the connection details to you. Any problems, please contact chembl-help@ebi.ac.uk.

I got a call from a tearful girl recently, saying " Daddy, I didn't know you did bad things at work " once over the initial shock, I thought what could she be talking about - did she know about the short-cut I use to get to the river to watch the trout?, or that I sometimes asked people in front of me in the queue for the coffee machine to get me a coffee to save my time at the inconsiderate expense of those in front of me? No, it was because I was involved in "Open Access" - lucky then she didn't know then that I was actually really working on a more extreme version - the more fundamentalist version that is the destroyer of capitalism - Open Data! ;) I said, " Princess, it's not that bad; honest; Daddy isn't a bad man ", she laughed at my distressed response, and then said " you should read the Daily Mail then ". This is what she had read. The Daily Mail is the most widely read UK newspaper, it also is a well...

The Teach-Discover-Treat (TDT) initiative was launched at the ACS meeting in San Diego under the umbrella of the Computers in Chemistry Division. The slides that describe the initiative are available on the website www.teach-discover-treat.org TDT aims to address outstanding gaps in drug discovery education and treatments for neglected diseases. A competition was launched that solicits submissions of computational models and tutorials for drug discovery for neglected diseases. All tools used for the computational workflows must be freely available (open source, free web servers, free download of executables) to enable global collaboration and innovation. There are 4 categories in the competition, and 4 awards!   Three of the categories are focused on specific neglected diseases for which datasets have been provided. Specific requirements have been formulated for the workflows that are to be the submissions for the competition in these three categories. Th...

Bissan and I just had a really good breakfast discussion on drugs, and it prompted me to do a picture for the blog. There'll be some more, depending on collecting glasses from the opticians, getting some ivermectin for the tick infections that have appeared on Vini and Bruce the bearded dragons (named after two of the major protagonists of the fantastic and situationist  durutti column ), the length of the queue of cars at the municipal tip in Sutton , and other weekend domestic stuff. Carbon and Oxygen are two essential life elements, and really important in drug structures - in fact, most drugs are 'organic' chemicals - those based on primarily on carbon chemistry. Carbon and oxygen can be combined in chemical reactions in various ways to give a number of compounds - they are all oxides of carbon. These are... Carbon dioxide - CO 2 - that well known environmental villain (and also life sustaining chemical) Carbon monoxide - CO - that well known poison (and a...

So, congratulations are in the air again - this time to Janet Thornton  (although the wikipedia page is now out of date), Director of the EMBL-EBI . Janet has just been awarded the British honour of Dame Commander of the Most Excellent Order of the British Empire (DBE) in the 2012 Queen's Birthday Honours list . This is absolutely fantastic news, and well done from all in the ChEMBL group. Many of you will already know Janet's fantastic track record of innovation in the study of protein structure, enzyme function, and more recently in some of the molecular processes of ageing - but Janet has also done great things in championing the sharing of biological data, and in encouraging sharing and collaboration on a global and international scale, for example via the establishment of the ELIXIR infrastructure. It's great to see her achievements and service recognised more broadly in society through this titular honour. Update : someone has updated the wikipedia page. C...

Congratulations to one of our collaborators, Paul Workman  FMedSci of the Institute of Cancer Research on being awarded the RSC Chemistry World Entrepreneuur of the Year award for 2012 . This award recognizes individuals that have made significant contributions to the commercialisation of science. Paul has of course got a fantastic record of significant scientific discovery in the area of molecularly targeted cancer research, but has consistently searched for ways of generating value and patient benefit from these by founding a number of companies to move these discoveries forward to potential therapies and products - spending time with Paul really makes clear the drive, belief and energy that's required to make a great scientific entrepreneur and innovator. Examples of his commercialisation of science include the founding of Piramed (acquired in a successful exit by Roche ) and Chroma Therapeutics . So well done Paul! And for readers of the blog interested in hearing some ...

ATC Code : L01XC13 Wikipedia : Pertuzumab On June 8th 2012, the US FDA approved pertuzumab (also known as RG-1273 and RhuMAb-2C4, tradename: Perjeta ) for the treatment of HER2/ERBB2 positive, late stage metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Breast cancer is the most common female cancer. About 20% of breast cancers have amplified and over expressed Epidermal Growth Factor Receptor 2 (EGFR2, a.k.a. ERBB2 and  HER2 ). These cancer subtypes are associated with worse prognosis and higher metastatic rates. Pertuzumab is an anti-ERBB2/HER2 recombinant humanized monoclonal. It has been approved for use as part of a triple combination containing pertuzumab, another anti-ERBB2/HER2 antibody, trastuzumab , and the taxane docetaxel . The added value of combining both anti-ERBB2/HER2 antibodies is that pertuzumab binds to a different part of ERBB2 - the extracellular dimerization domain (Subdomain II...

There's a paper just published in Nature getting a lot of coverage on the internet at the moment from Novartis/UCSF, and for good reason - but as the cartoon above states, it will probably have less impact than news on Justin Bieber's new haircut, or the latest handbags from Christian Lacroix. It uses the SEA target prediction method, trained using ChEMBL bioactivity data in order to predict new targets (and then by association side effects) for existing drugs. These are then experimentally tested, and the results confirmed in a number of cases - this experimental validation is clearly complex and expensive, so it is great news that in silico methods can start to generate realistic and testable hypotheses for adverse drug reactions (there are also positive side effects too, and these are pretty interesting to look for using these methods as well). The use of SEA as the target prediction method was inevitable given the authors involved, but following up on some presenta...

Links to ChEMBL compounds from wikipedia have been there for some time, and now there is the target equivalent - for example here is the link to human thrombin .

So, some more stuff on assays, in my quest to have something different to speak about over the summer; this post is about the tests a compound needs to pass through before it can become a drug. For a real test case, none of those green and red blobs I normally talk about, I took the excellent paper published in Science a few years ago - this is a great paper, discovering a clinical candidate for the treatment of malaria from a natural product screen. NITD609 is currently in phase 1 trials . %T Spiroindolones, a Potent Compound Class for the Treatment of Malaria %J Science %D 2010 %V 329 %P 1175-1180 %O DOI: 10.1126/science.1193225 %A M. Rottmann %A C. McNamara %A B.K.S. Yeung %A M.C.S. Lee %A B. Zou %A B. Russell %A P. Seitz %A D.M. Plouffe %A N.V. Dharia %A J. Tan %A S.B. Cohen %A K.R. Spencer %A G.E. González-Páez %A S.B. Lakshminarayana %A A. Goh %A R. Suwanarusk %A T. Jegla %A E.K. Schmitt %A H.-P. Beck %A R. Brun %A F. Nosten %A L. Renia %A V. Dartois %A T.H. Keller %A D....

Here is a link to a Google Scholar page  detailing papers that cite the NAR Database paper of Gaulton et al . We'll try and assemble these into an archive (for the Open Access ones only of course) somewhere into our plans on the new ChEMBL interface.