Spring 2015 Newsletter

Spring 2015 Newsletter

Welcome to the Spring 2015 Newsletter from CompChem Solutions Limited.

In this edition we focus on the emergence of epigenetics as a key area of research for many therapeutic endpoints and describe some of our fixed-fee services for epigenetics research, and there is a brief review of the recent Spring Meeting of the UK QSAR and Chemoinformatics Group in Leeds.  And of course, we cover some upcoming events and jobs which may be of interest to our readers.  Our new In Brief section is a short round-up of news items from CompChem Solutions.

 In Brief

  • We currently have consultants readily available for interim work to cover short-term requirements for computational chemistry and computational biology resource, including maternity cover, helping to manage peaks in demand for CRO computational scientists and plugging the resource gap whilst recruitment of permanent staff is underway.  See our previous article on interim cover to find out how it could help your organisation, or  contact us for more information.
  • We’re looking forward to the Cresset European User Group Meeting later this week – it sounds like a good one!  Come and meet us there.  We’ll also be at the SCI/RSC Medicinal Chemistry Symposium in September.
  • We have lots of upcoming publications in the pipeline, covering some nice med chem case histories, some novel structural biology, and a book chapter on applied biophysics related to protein-protein interactions.  Watch this space in the coming months!


Epigenetics – To Individuality & Beyond?

Epigenetics seems to have become of of the key buzzwords amongst the research community recently, but what exactly is it, and why should we be interested in it?  Despite various historical uses of the term, the modern use and interpretation has been narrowed to describe the study of changes in gene expression patterns which are are not caused by changes in DNA sequence.  DNA in cells is wrapped around histones, and these units are punctuated by “epigenetic tags”, creating a unique “epigenome” in each living organism.  The epigenome can be influenced by many factors, such as diet, stress, hormone levels and lifestyle choices, and the output from this is that expression levels of certain genes will be increased or decreased according to each individual epigenome.

Although research in the area really kicked off in the mid-1990s, it is believed that the key processes involved are only recently beginning to be understood.  Current therapeutic intervention has focused around targets involved in reading of the epigenome (covering > 26 families of proteins, including bromodomains, MBTs and PHDs), writing the epigenetic codes (eg histone acetylases, lysine methyltransferases, protein argenine methyltransferases) and erasing epigenetic codes (eg HDACs and KDMs).  Small molecule inhibitors are already known for all three intervention strategies, amongst those a DOT1L inhibitor (a histone KMT epigenetic writer target) , EPZ-5676, being in Phase I clinical trials for leukaemia, an EZH2 inhibitor (EPZ6438) being in Phase II/III clinical trials for non-Hodgkins lymphoma, GSK525768A (an inhibitor of the tandem bromodomains of BET) being progressed to the clinic,  trialling against various carcinomas.

The main focus of most epigenetic research has been in oncology, but inflammatory conditions, autism, syndromes arising from chromosome instability (eg Fragile-X), mental retardation syndromes (eg Angelman’s Syndrome) and many other conditions are also thought to be related to epigenetic changes.

Whilst various online resources such as NCBI Epigenomics, the Human Epigenetic Enzyme & Modulator Database, HEMD, ChEpiMod, ChromoHub from the SGC  and sections of Chembl can be useful for exploring target/phylogenetic information on epigenetic proteins and their inhibitors, a database of known epigenetic small molecule inhibitors has only recently been reported.  This should facilitate small molecule research in epigenetics.

With a new round of BBSRC funding in the area about to be announced, this is sure to be a hugely active area of research going forward.  CompChem Solutions can provide computational biology services to assist epigenetics research, as well as computational chemistry services to assist in all aspects of small molecule approaches towards these targets.  To learn more about some specific epigenetics packages we offer, do read on to the section below, but remember that we can assist with many more approaches towards the discovery of epigenetically active therapeutics, including selectivity studies, rational ligand design, scaffold hopping and ligand-based approaches.  Contact us for more information.


Epigenetics Packages from CompChem Solutions Ltd

To assist with the quest for novel epigenetics modulators, CompChem Solutions can offer fixed price packages covering:

  • Virtual screening of a database of known small molecule inhibitors against your epigenetic protein target(s), where the structure of the target(s) is known or can be modelled, coupled with scaffold-hopping approaches and/or similarity searching against commercially available screening compound sets to identify small molecules to synthesise or to purchase.
  • Field-based or standard pharmacophoric model building for epigenetic targets where the protein target information is not known or not able to be modelled, coupled with scaffold-hopping approaches and/or similarity searching against commercially available screening compound sets to identify small molecules to synthesise or to purchase.
  • Protein sequence and structural alignment studies to identify likely selectivity issues and routes to potentially overcome these.

Contact us for more information.


Spring in Leeds –

The Recent UK-QSAR & Chemoinformatics Group Meeting Blew Us Away!

On a particularly blustery day last month, the UK-QSAR & Chemoinformaics Group descended on Lhasa Ltd in Leeds for a Spring Meeting focused on toxicology and metabolism.  It turns out that Lhasa is based opposite the highest building in Leeds, the Bridgewater Centre, which is notorious for causing a “wind tunnel” effect and has been blamed for several “incidents” in recent years (http://www.bbc.co.uk/news/uk-england-leeds-21633206) but thankfully for Lhasa, and indeed the general population of Leeds, it sounds like plans are underway to tackle the problems for the future.  The cold northerly blast didn’t, however, detract from the warm hospitality served up by Lhasa to the meeting delegates.

The morning session covered a good range of topics in toxicology, from Nora Aptula’s prespective on the use of “read-across” to extrapolate tox data on new chemicals based on that of known analogues, thereby reducing animal testing, to Tim Allen’s (University of Cambridge) description of an “atlas”of Molecular Initiating Events  to help predict toxicological outcomes (http://tt21c.org/wp-content/uploads/2014/01/Towards-an-MIE-Atlas-FutureToxII.pdf).

The afternoon session on metabolism covered a talk from Lhasa on a machine-learning system to rank metabolites, an overview of current experimental and computational approaches to predicting metabolism from Johannes Kirchmair and a QSAR approach (surprisingly unusual for a UK-QSAR & Chemoinformatics Group Meeting talk!) for metabolic engineering (ie generation) of specific metabolites from Jean-Loup Faulon (Manchester Institute of Biotechnology).

The afternoon was rounded off with a new concept for these meetings – a panel discussion, chaired by Chris Barber of Lhasa.  Audience participation was enthusiastic and some very thoughtful questions were posed.

Congratulations are due to Lauren Reid of MedChemica who won the poster prize, and huge thanks go out to Lhasa for their generous welcome and sponsorship of the event.  The autumn meeting will be in Duxford on 6th October 2015, hosted by Cresset.  We look forward to it!



Cresset European User Group Meeting, 18th June 2015, Madingley Hall, Cambridge

2nd Epigenetics Symposium, 3rd July 2015, Cambridge

Cambridge Chemoinformatics Network Meeting, 26th August 2015, Cambridge Centre for Molecular Informatics

18th SCI/RSC Medicinal Chemistry Symposium, September 13-16 2015, Cambridge

UK-QSAR and Chemoinformatics Autumn Meeting, October 6th 2015, Duxford, Cambridge



Computational Chemistry Developer, Cresset Ltd, Herts, UK

Scientific Programmer/Bioinformatician, Healx, Cambridge, UK

Senior Scientist Computational Chemistry, Proteros Biosciences GmbH, Martinsreid, Germany

Computational Chemist, Boehringer Ingelheim, Vienna, Austria

Graduate Chemoinformatics Scientist, Medchemica Ltd, Macclesfield, UK

Senior Scientist Chemoinformatics, UCB Ltd, Slough, UK

Post Doc in Chemogenomics modelling,   Chemistry Innovation Centre of AstraZeneca, Molndal, Sweden










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