The ChEMBL-og

We have just had a paper accepted in PLoS Computational Biology on the work we've done on allosteric modulators (first mentioned on the blog  here ).  The work is based on the mining of allosteric bioactivity points from ChEMBL_14. The data set of allosteric and non-allosteric interactions is available on our FTP site ( here ). This blogpost will just highlight some sections of the paper, but we would like to refer the interested reader to the full paper ( here ).  Dataset The dataset contains ChEMBL annotated and cleaned data divided in both an 'allosteric' set and a 'non-allosteric' (or background) set. Abstracts and titles mentioning allosteric keywords were pulled and from the resulting papers we extracted the primary target and all bioactivities on this primary target. From the remainder of the papers we also retrieved the primary target and all bioactivities on this primary target in a similar manner.  Targets When we observed the target distr...

On April 30th 2014 the University of Strathclyde will host a seminar on Allosteric Drug Design organised by the smsdrug.net collaboration. The goal of the seminar is to bring together academic and industrial researchers with an interest in allosteric drug design and development with a view to identifying future collaborative and funding opportunities. The seminar consists of a series of three talks by : Dr. Gerard JP van Westen (EMBL-EBI ; ChEMBL), Prof. Dr. Leonardo Scapozza (University of Geneva) and Dr. Laurent Galibert (Alpine Institute for Drug Discovery). The talks will cover various of drug design in relation to allosteric drug targets. Talks are aimed at a broad audience. To register and for further information please go to www.engage.strath.ac.uk/event/125/

For many classically 'undruggable' targets, there is sometimes the prospect of the discovery and optimisation of allosteric regulators, these can offer advantages in more selective target regulation, or improve the drug-like properties of compounds that bind to the allosteric site. However, allosteric regulators are often discovered via serendipity, and many screens are not configured optimally to identify allosteric regulators. As part of the SMSdrug.net grant we are involved in, there is an Allostery Workshop taking place at the University of Edinburgh on 4th December 2012 . The Workshop, sponsored by the British Council, involves an extensive delegation of scientists from Turkey led by Burak Erman, Koc University , Istanbul and will bring together a diverse area of disciplines including Biology, Chemistry, Computer Science, Informatics, Mathematics and Medicine. The program for the day will include presentations and poster session. Gerard Van Westen from the group...

ATC Code : N03AX22 Wikipedia : Perampanel On October 22nd 2012 the FDA approved Perampanel (research code: E2007, ER-155055-90, trade name Fycompa, CHEMBL1214124 ). Perampanel is an orally administered drug to be used as an adjunctive therapy for the treatment of partial-onset seizures with or without secondary generalized seizures in patients with epilepsy . Epileptic seizures are defined as "abnormal excessive or synchronous neuronal activity in the brain". The net symptoms can be very diverse, from severe thrashing movements to a very mild brief loss of awareness. Approximately 4% of the population will have experienced a unprovoked seizure by the age of 80, with a 30-50% chance of repeat in this group. Seizures can last from a few seconds to a state of life threatening persistent seizure (known as status epilepticus ). Approximately 25 % of the people suffering from a seizure or  status epilepticus will be diagnosed to ...

When a screen and follow-up have failed to deliver an attractive lead for a 'hard' target, talk amongst the team often turns to running a screen for an allosteric inhibitor; Allosteric regulators are therefore a seductive/tantalising approach to find leads against tough targets such as protein-protein interactions, highly polar binding sites, etc . But, there's a few hard questions to answer, this is just a few. Just how do I run a screen for an allosteric inhibitor? What compounds do I select for allosteric sites? How likely am I to find an allosteric inhibitor?  What sorts of targets can be allosterically modulated? What are the 3-D properties of allosteric sites I've read some of the literature behind the arguments for allosteric inhibitors, and I must say I'm not that convinced as to their general potential benefits at the moment - of course in some cases, they will be perfect, but are the advantages as general as people may think. But I've been...