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Showing posts from November, 2012

ChEMBL Cross Reference Links Now In UniProt

So, some great news for those of you that use UniProt - there are now links to the corresponding target pages in ChEMBL in there.

Here's the link (http://www.uniprot.org/uniprot/?query=database%3AChEMBL&sort=score) to the list of ChEMBL targets that are in Uniprot. And there are links to ChEMBL in the Cross References section.

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A 101 Thankyou's!

This week, our ChEMBL NAR Database paper made the milestone of over a hundred citations (in less than a year too). This made us all very, very happy, and for a few moments, we rested our fingers from our keyboards, and used our them instead to grasp a mug of coffee/tea; but only for a few seconds, before we got back to mixing and baking and cooking ChEMBL 15 for you all.

Here's a list to the current citations of Gaulton et al., NAR Database, 40, D1100-D1107, 2012. Remember this is an Open Access paper.

Please keep, keeping us happy by using our work, it's probably the biggest satisfaction we can get :)

ChEMBL At SWAT4LS

As part of the ChEMBL groups involvement in the OpenPhacts project, a representative from the ChEMBL team will be attending SWAT4LS next week. As well as hacking and learning about new Semantic technologies there may be time to catch up with ChEMBL users also attending the workshop. So if you would like to hear about what we are doing with the Semantic Web, RDF or just have a general chat about ChEMBL, please get in touch.

New Drug Approvals 2012 - Pt. XXV - Tofacitinib citrate (XELJANZ®)

On November 6, the FDA approvedTofacitinib citrate (Trade Name: XELJANZ®; Research code: CP-690550, ChEMBL : CHEMBL221959, PubChem: CID9926791, DrugBank: DB08183, ChemSpider: 8102425) to treat moderately to severely active Rheumatoid Arthritis (RA). It is orally administered and may be used as monotherapy agent or in combination of non-biologic DMARDs. About 1% of the world-wide population is affected by rheumatoid arthritis. RA affects predominantly women (three times more susceptible than men) and is more frequent between ages 40 and 50, but people of any age can be affected.
Other approved drugs in this commercially competitive sector include Adalimumab (Trade Name:Humira, ChEMBL: CHEMBL1201580, DrugBank: DB00051), Etanercept (Trade Name: Enbrel, ChEMBL: CHEMBL1201572, DrugBank: DB00005), Infliximab (Trade Name: Remicade, ChEMBL: CHEMBL1201581, DrugBank: DB00065).

IUPAC Name: 3-(4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile Canionical Smi…

ChEMBL VM

The testing and QC pixies have been really busy with Open ChEMBL - the OSDODS virtual machine appliance - this has made us aware of the support questions we're likely to get, and so we'd like to build our knowledge-base of support issues with a small pilot release, prior to facing a lot of queries about VirtualBox, ifconfig etc.

If you are interested in getting early access to Open ChEMBL, and have experience in configuration of vm's in heterogeneous environments - please get in touch.

DNDi screens MMV’s open access Malaria Box

The Drugs for Neglected Diseases initiative (DNDi) and Medicines for Malaria Venture (MMV) announce today the identification of three chemical series targeting the treatment of deadly neglected tropical diseases (NTDs), through DNDi’s screening of MMV’s open access Malaria Box. The resulting DNDi screening data are among the first data generated on the Malaria Box to be released into the public domain, exemplifying the potential of openly sharing drug development data for neglected patients.

The open access Malaria Box is an MMV initiative launched in December 2011 to catalyse drug discovery for malaria and neglected diseases. It contains 400 molecules, selected by experienced medicinal chemists to offer the broadest chemical diversity possible and is available free of charge. In return, MMV requests that any data gleaned from research on the Malaria Box are shared in the public domain within two years. To date, more than 100 Malaria Boxes have been delivered to over 20 countries fo…

SMS-DrugNet Allosteric Regulators Workshop, Edinburgh, December 2012.

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 here will …

ChEMBL Virtual Machine

Next week we will be releasing ChEMBL Virtual Machine. We have referred to it in a previous post and had hoped to make it available this week, but as always with best laid plans....

So, we are using this post to generate some pre-release excitement :) and also to acknowledge the hard work of Rodrigo Ochoa who worked on this project during his 5 month internship with the ChEMBL group.

We will be providing a lot more detail in next weeks blog post, but as a quick summary the VM is based on a Ubuntu linux build and comes preloaded with ChEMBL_14 (in PostgreSQL), RDKit and a web application, which makes use of Marvin and allows users to easily get started with querying the ChEMBL data.

New Drug Approvals 2012 - Pt. XXIV - Ocriplasmin (JetreaTM)

On October 17, the FDA approved Ocriplasmin (tradename: Jetrea; Research Code: Microplasmin), a proteolytic enzyme indicated for the treatment of symptomatic vitreomacular adhesion (VMA). VMA is a condition of the eye that results from the liquefaction of the vitreous gel within the human eye and consequent adhesion to the retina. As the eye ages, the vitreous humor can naturally separate from the retina. However, if the separation is not complete, areas of adhesion can occur. The traction from these adhesion areas on the retinal surface is the underlying pathology of symptomatic VMA, which can lead to ocular damage. Ocriplasmin is the first drug approved to treat this condition and it exherts its therapeutic action by selectively breaking down the three major protein components, fibronectin, laminin and collagen, of the vitreous body and vitreoretinal interface, and thereby dissolving the protein matrix responsible for VMA. The only alternative treatment is a surgical procedure to r…

New Drug Approvals 2012 - Pt. XXIII - Omacetaxine mepesuccinate (SYNRIBOTM)

ATC code: L01XX40
Wikipedia: Omacetaxine_mepesuccinate

On October 22nd 2012 the FDA approved omacetaxine mepesuccinate (research code: CGX-635, trivial name: Homoharringtonine, trademark: SynriboTM) for the treatment of chronic or accelerated phase chronic myeloid leukaemia (CML) in adults with resistance to two or more tyrosine kinase inhibitors. Omacetaxine is an old drug identified 35 years ago and known to have activity in CML, but its clinical development was previously halted due to the discovery of BCL-ABL and other targeted kinase inhibitors Pubmed: 21294709. The rapid development of tyrosine kinase inhibitor resistant tumors has led to the need for agents that can act in these treatment-derived drug-resistant patients. Omacetaxine mepesuccinate has been approved based on observed major cytogenetic response rather than on improvement in disease-related symptoms or increased survival.


Omacetaxine mepesuccinate/homoharringtonine is a cephalotaxine ester of prepared by a semi-synt…

Paper: Mapping small molecule binding data to structural domains

We've just published a paper on mapping the sites of small molecule binding in complex multidomain proteins (pdf here - this link doesn't seem to work at the moment, sorry). The resolution of the mapping is at the level of Pfam domains. We love Pfam, and love it even more that the Pfam team is moving to the EBI this week. The motivation for this work is multifold, and it addresses a pretty big problem in chemogenomics.

Firstly the issue of domain frustration - you search a protein containing a series of distinct domains looking for homologues in ChEMBL. If your protein contains a common and uninteresting domain, something like a zinc finger or EGF domain (our interest is for small molecule binding remember, we're not saying that these domains are completely boring, they're just a lot less interesting from a chemical biology/drug discovery perspective) you'll retrieve a whole bunch of sequence related, but small molecule binding unrelated data. It's just the wa…

New Drug Approvals 2012 - Pt. XXII - Perampanel (FycompaTM)

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 have epilepsy. Treatment may reduce the…