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Showing posts from August, 2011

MIABE - Minimum Information about a Bioactive Entity

Minimum Information Standards are an important feature in many aspects of science, and there is a rich history of the success of these in encouraging data interoperability across scientific resources and data analysis. An opinion paper has just been published in NRDD, that discusses bioactivity data. The paper itself seems to be open access (from my hotel room at least) - the link is here.

%T Minimum information about a bioactive entity (MIABE)%J Nature Reviews Drug Discovery %V 10 %P 661-669 %D 2011 %A S. Orchard %A B. Al-Lazikani %A S. Bryant %A D. Clark %A E. Calder %A I. Dix %A O. Engkvist %A M. Forster %A A. Gaulton %A M. Gilson %A R. Glen %A M. Grigorov %A K. Hammond-Kosack %A L. Harland %A A. Hopkins %A C. Larminie %A N. Lynch %A R. K. Mann %A P. Murray-Rust %A E. Lo Piparo %A C. Southan %A C. Steinbeck %A D. Wishart %A H. Hermjakob %A J. Overington %A J. Thornton %O doi:10.1038/nrd3503

New Drug Approvals 2011 - Pt. XXVI - Icatibant (FirazyrTM)

ATCC: C01EB19 Wikipedia: Icatibant
On the August 25th 2011, the FDA approved Icatibant (trade name: FirazyrTM), a bradykinin B2 receptor (B2R)antagonist indicated for the treatment of acute attacks of hereditary angioedema (HAE) in patients aged 18 or older.


HAE is a rare genetic disease and is caused by low levels of C1-esterase inhibitor (C1-INH), the major endogenous inhibitor and regulator of the protease plasma kallikrein and the key regulator of the Factor XII/kallikrein cascade. One component this cascade is the production of bradykinin by plasma kallikrein. During HAE attacks, disregulated activity of plasma kallikrein leads to excessive bradykinin production; bradykinin is a potent vasodilator, which s thought to be responsible for the characteristic HAE symptoms of localised swelling, inflammation and pain.

Icatibant treats the clinical symptoms of HAE attack by selective- and competitively binding, as an antagonist, to the B2 bradykinin receptor (B2R) (Uniprot: P30411; ChEMBL I…

New Drug Approvals 2011 - Pt. XXV crizotinib (Xalkori®)

ATCC: L01XE15 Wikipedia: Crizotinib
On the August 26th 2011, the FDA approved crizotinib (trade name:Xalkori® Research code: PF-02341066), an anaplastic lymphoma kinase (ALK) inhibitor for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is ALK-positive as detected by an approved FDA-approved test.


Non-small cell lung carcinomas (NSCLC) are cancers of the epithelial cells in the lung and describe all types of lung carcinomas other than small cell carcinomas. NSCLCs make up 88% of all lung carcinomas (see Cancer Research UK pages) and comprise genetically distinct classes of cancer, the most common are: Lung adenocarcinoma, large cell carcinoma and squamous cell carcinoma. Across the NSCLC types, some tumors harbour an ALK fusion protein. The EML4-ALK fusion gene has been shown to be affect the outcome of drug response and cells show resistance to EGFR inhibitors.


Crizotinib is an orally-dosed receptor tyrosine kinase inhibitor with si…

ChEMBL-og NME Approval Monographs now on ChEMBL site

We've added a cumulative list of the ChEMBL-og drug monographs to the ChEMBL web interface. As new drugs, more specifically new molecular entities (NMES)) are approved (currently in the US) we write a short, consistent monograph on each approval. Coverage is from 2009 onwards. These typically appear a few days after the approval. We also provide a set of assignments (Rule of Five, Chiral, Black Box Warnings, etc.) for each drug. Some of these assignments are subjective, for example assigning a drug as natural product-derived is sometimes challenging.

We try to keep these current, so there will be inconsistency between the views through the ChEMBL interface and on this page, but this is currently inevitable in our versioned release of ChEMBL.

Any feedback on the view, data, etc. would be gratefully received.

ChEMBL Release Scheduling

We are currently reviewing our internal release process for ChEMBL, and have a question. When we do a release, there are sometimes changes to the schema (we generally detail these in the release notes of previous releases) and also changes to deprecated items (targets or compounds that have changed or disappeared). We now also have a series of sites that use the ChEMBL data to provide new services, and these will invariably break (often both in and outbound links) as loading and processing of the ChEMBL data happens in these other systems.

One of the ideas we are considering is to have a 'pre-release' of the forthcoming release to interested parties during our normal one or two week long testing period. This could allow a smoother release schedule, and also help us with support issues after releases, but I'm sure have some further problems for us. So, if you run a resource, using ChEMBL and would like to discuss this with us, or if you have other views, we'd be happy t…

PhD studentship Available for Oct 2012 Intake

We will be recruiting a PhD student to start in October 2012. Details of the application process can be found at www.embl.org/phdprogramme. The deadlines are important - you will need to register by December 1st 2011, with a final deadline of 12th December 2011.
There is a lot of exciting research in chemical biology at EMBL, and ideas for potential PhD projects within the chembl group include:
Design of biopharmaceuticals using rule-based approaches.Drug design strategies to improve drug safety.Multi-scale indexing, visualisation and navigation of chemical structures.Drug attrition analysed using systems biology and simulation approaches.

However, we would be really keen to discuss your interests if you do apply. Contact us if you wish to discuss anything.

ChEMBL Identifiers

A few notes about the use and format of identifiers in ChEMBL:

Each of the major entity types within ChEMBL (documents, assays, compounds and targets) are assigned unique ChEMBL identifiers, which take the form of a ‘CHEMBL’ prefix followed immediately by an integer (e.g., CHEMBL25 is the compound aspirin, CHEMBL210 is the human beta-2 adrenergic receptor "target"). There is no distinction between the format of the identifier for different types of entities, but a given ChEMBL identifier will only ever be assigned to a single entity (i.e., CHEMBL25 will only ever be used for the compound aspirin and never for an assay, document or target). A lookup table is provided in the database, to resolve which identifiers correspond to which entity types.
ChEMBL identifiers are stable with respect to the entities they represent. For compounds (with known/defined structures), ChEMBL identifiers represent distinct compound structures, as defined by the standard InChI, e.g., CHEMBL25 repre…

New Drug Approvals 2011 - Pt. XXIV Vemurafenib (Zelboraf TM)

ATC code: L01XE15 Wikipedia: Vemurafenib
On the August 17th 2011, the FDA approved Vemurafenib (trade name:ZelborafTM Research code: PLX-4032, RG-7204 and RO-5185426), a BRAF kinase inhibitor for the treatment of patients with unresectable or metastatic melanoma carrying the mutant BRAFV600E.

Melanoma is a malignant tumor of melanocytes (skin cells that produce melanin) and is an aggressive disease responsible for an estimated 50,000 deaths worldwide. Over 50% of patients with advanced melanoma carry an activating mutation in the Serine/Theronine protein kinase: BRAF (V600E).
The MAPK signal transduction pathway is an important and frequently mutated pathway in cancer. A wide variety of growth factors signal through this pathway, via RAS and RAF proteins to cause cell proliferation. The activating mutation in BRAF causes activation of this pathway downstream of BRAF regardless of the presence of growth factor (the signalling pathway is 'dysregulated'). The protein of Vemuraf…

New Drug Approvals 2011 - Pt. XXV Brentuximab vedotin (AdcetrisTM)

ATC code:L01XC12
On 19th August 2011, the FDA approved Brentuximab vedotin (trade name AdcetrisTM, ATC code:L01XC12, research code:SGN-35, aAC10-vcMMAE), a antibody drug conjugate (ADC) targeting CD-30, indicated for the treatment of patients with Hodgkin's lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates (1.1); and the treatment of patients with systemic anapaestic large-cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen.

Hodgkin's lymphoma is a cancer of cells derived from white blood cells called lymphocytes. In Hodgkin's lymphoma, the disease spreads from one lymph node group to another, and then leads to more systemic effects. Hodgkin's lymphoma can be treated with radiation therapy, chemotherapy or autologous hematopoietic stem cell transplantation. The occurrence of the disease shows two age peaks: the…

Drug Repurposing: Screening of known drugs against malaria

Just a quick (but surprisingly wordy) follow up on the previous post on the drug profiling against malaria. Drug repurposing/reuse/rescue offers great potential for the enhancement of patient lives and also is a quick way of pushing new therapies through the clinic. It is often see as low cost and low risk, is highly translational in terms of the research, and there are some stunning success stories. It is therefore very sensible to screen known drugs in assays of interest, which is exactly what was done in the recent, excellent, Science paper.

The compounds in Table 1 of the paper are reported at the highly active set (and these exclude already known established antimalarial drugs which all pass the selection criteria used for compounds in this table, this seems a pretty good and pragmatic place to set cutoffs). For use as an widely-used and developing world-applicable antimalarial (co)-therapy I would have imagined that ideally you would want established well tolerated daily dosing…