ChEMBL Resources

The SARfaris: GPCR, Kinase, ADME

Monday, 30 April 2012

Last chance to sign up for the webinar on Web Services - 2nd May

This is a last chance call for people who want to sign up for the "Web Services" webinar that will be hosted this Wednesday 2nd May at 3.30pm (GMT+1).

It will be a 45 minute webinar that will take you through the ChEMBL web services.

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

The poll will be closed tomorrow, 1st May to allow us to send out the connection details to the attendees.

Tuesday, 24 April 2012

Bio-IT World, Boston

Today, I (Louisa) gave a workshop talk at the Bio-IT World Expo in Boston. The title of the talk was 'Curating and Mapping the Drug Name Space in ChEMBL'. This expo is being held at the Boston World Trade Center, which is a great location right on the waterfront. It is the 10th anniversary of the expo, so I am expecting the rest of the conference to be very interesting and I have already tagged some talks that I definitely want to go to.

Friday, 20 April 2012

Canadian Bioinformatics Workshop

Yesterday, I gave a tutorial in Toronto, Canada on how to use the EBI chemical entities databases as part of the 'Patent Informatics: Sequence & Chemical Databases for Prior Art Searching' workshop. This one day session was organised by the Canadian Bioinformatics Workshop. It was held at the Ontario Institute for Cancer Research, which is situated in downtown Toronto. It was a very well organised workshop with good facilities and tasty refreshments. Toronto is a beautiful city and I hope to explore it tomorrow before flying down to Boston to give my talk at Bio-IT World.

Thursday, 19 April 2012

New Drug Approvals 2012 - Pt. IX - Florbetapir F 18 (AmyvidTM)

ATC code: V09AX05 (incomplete)

On April 6th, FDA approved Amyvid (Florbetapir F 18), a radiolabeled intravenous imaging agent for the differential diagnosis of Alzheimer's Disease.

Alzheimer's Disease (OMIM 104300, MeSH D000544) is a non-treatable, progressively worsening and fatal disease and the main cause of dementia.
Most commonly affecting the elderly (>65y), it correlates with the growing deposits of aggregating beta amyloid (UniProt P05067) fibrils in the brain, eventually physically destroying it, and abnormal aggregation of the tau protein (UniProt P10636), a microtubule-associated protein inside neurons.
Early symptoms of Alzheimer's include impairment of short term memory, advanced ones, irritability, confusion, aggression, mood swings, and long term memory loss, amongst others.

Diagnosis of Alzheimer's is complicated by overlap of symptoms with other cognitive diseases, and "normal" signs of ageing; sometimes, only brain autopsy (necessarily posthumous) can confirm its presence, while, conversely, patients displaying typical Alzheimer's symptoms sometimes don't show its physiological manifestation. Differential diagnostic techniques include detection of (amongst other biomarkers) amyloid or tau proteins in the spinal fluid, and brain imaging using Positron Emission Tomography (PET), with or without contrast enhancing agents, i.e. radionuclides. A drawback of an early such compound, Pittsburgh compound B (PiB, ChEMBL ID CHEMBL207456, PubChem 2826731), is the short half life (~20 minutes) of the carbon isotope (11C) included. Florbetapir, on the other hand, has a radioactive fluorine isotope (18F) with a half life of ~2 hours, improving its handling and signal strength.

It has to be noted that the presence of plaques, e.g. visualized by PET, and potentially aided by Florbetapir, does not necessarily and sufficiently indicate Alzheimer's; plaques may be present in patients with other neurological disorders, or elderly people with normal cognition. However the absence of significant plaques may rule out the possibility of a patient suffering from Alzheimer's.

Florbetapir (ChEMBL ID CHEMBL1774461, PubChem 24822371) is a radiocompound with molecular weight 360.4 Da, ALogP 3.14, 1 hydrogen bond donor, 4 hydrogen bond acceptors, and thus fully rule of five compliant. It possesses a radioactive isotope of fluorine, 18F, and a C=C double bond in trans / E configuration.
Its systematic (IUPAC) name is 4-[(E)-2-[6-[2-[2-(2-fluoranylethoxy)ethoxy]ethoxy]pyridin-3-yl]ethenyl]-N-methylaniline, Canonical SMILES CNc1ccc(\C=C\c2ccc(OCCOCCOCC[18F])nc2)cc1, Standard InChI=1S/C20H25FN2O3/c1-22-19-7-4-17(5-8-19)2-3-18-6-9-20(23-16-18)26-15-14-25-13-12-24-11-10-21/h2-9,16,22H,10-15H2,1H3/b3-2+/i21-1.

After injection of Amyvid as a single recommended dose of 370 MBq, the agent passes the blood brain barrier and accumulates at amyloid plaques in the patient's brain. 30 to 50 minutes post injection, a 10 minute PET image is acquired.

It is unknown whether Amyvid affects reproductive capacity or causes fetal harm, or whether it is secreted in human milk, but it is not recommended to be used in the respective population. The agent is not indicated for use in pediatric patients. Majority of clinical studies subjects being elderly, no overall differences in safety or effectiveness between them and younger subjects were observed. Because of the agent being radioactive, special precautions have to be taken retrieving, transporting, and administering the agent. The radiation absorbed dose from a single Amyvid dose is 7 mSv in an adult and thus comparable to a chest CT scan, or about twice the normal yearly background dose.
Notable adverse reactions include headache (<2% of patients), musculoskeletal pain, fatigue, nausea (<1%), and anxiety, back pain, increased blood pressure, claustrophobia, feeling cold, insomnia, and neck pain (<0.5%). In early 2011, FDA recommended against approval of Florbetapir, unless structured training programmes for PET readers using Florbetapir would be provided; latest clinical trials of Florbetapir include data from readers either trained manually, or electronically, both proving to be effective.

Amyvid has been developed by Eli Lilly and Company, and Avid Radiopharmaceuticals Inc., its wholly owned subsidiary, and is marketed by Lilly.

The full prescribing information can be found here.

Tuesday, 17 April 2012

ChEMBL Workflows for medicinal chemists workshop

On Friday 11th May 2012 we are running a small (and free) interactive workshop on "Shaping the Future of ChEMBL".  We would like your input to develop some easy to use workflows for several key tasks that drug discoverers often want to do, and could do more efficiently with the ChEMBL data.  These workflows would be aimed at medicinal chemists and would cover the use of ChEMBL data in lead generation and optimization tasks, hence we would like to involve medicinal chemists in their creation and implementation.  

The workshop will be on campus here at Hinxton, and will start around 10am and finish around 3pm (lunch, coffee and cakes will be provided).

If you are interested in helping, with what will hopefully be a fun day, please contact us.

Thursday, 12 April 2012

Interface & Searching Webinar 18th April

This is a call for people wanting to sign up for the "Interface & Searching" webinar that will be hosted next Wednesday 18th April at 3.30pm (GMT).
It will be a 45 minute webinar that will take you through the ChEMBL interface and schema, showing you how to navigate the data and how the tables are all connected.
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
For those of you who can't make it to this webinar, we will be hosting it again on the 13th June.

Monday, 9 April 2012

Joint EMBL-EBI and WT Resources for Computational Drug Discovery Course - 2-6 July 2012

This joint EBI-Wellcome Trust course aims to provide the participants with the principles of chemical biology and how to use computational methods to probe, explore and modulate biological systems using chemical tools. The course will be comprised of a mixture of lectures and hands-on components. The conceptual framework will be covered, as well as direct practical experience of retrieving and analysing chemogenomics data. Participants will be able to do their own target analysis and identify appropriate chemical tools for probing biological systems of interest to them.

Check out more details on the link above.

Thursday, 5 April 2012

We all know just how useless HTS is, don't we?

Well, there's a great paper in a recent Nature Reviews Drug Discovery from a cross-industry set of authors on a retrospective analysis of HTS in drug discovery - lots of data, lots of examples, and a balanced argument for the case for high-throughput screening in modern pharmaceutical discovery.

%T Impact of high-throughput screening in biomedical research
%J Nature Rev. Drug Disc.
%V 10
%D 2012 
%P 188-195
%A R. Macarron
%A M.N. Banks
%A D. Bojanic
%A D.J. Burns
%A D.A. Cirovic
%A T. Garyantes
%A D.V.S. Green
%A R.P. Hertzberg
%A W.P. Janzen
%A J.W. Paslay
%A U. Schopfer
%A G.S. Sittampalam

Monday, 2 April 2012

New Drug Approvals 2012 - Pt. VIII - Peginesatide (OmontysTM)

ATC code: B03XA (incomplete)

On March 27, the FDA approved Peginesatide for the treatment of anemia due to chronic kindney disease (CDK) in patients on dialysis. CDK is a slow but progressive loss of kidney function that can be caused by diabetes mellitushypertension and glomerulonephritis, among others. One of the symptoms in the advanced stages of CDK is anemia, a decrease in the number of red blood cells and hence the hemoglobin (adult hemoglobin: heterotetramer of two copies of P69905 and two copies of P68871) content of the blood. Anemia in patients suffering from CDK is caused by reduced production of erythropoetin, a hormone that regulates the levels of red blood cells and is synthesized predominantly in the cortex of the kidney.

Anemia induced by CDK can be treated by supplying exogenous erythroepotin or analogs of this hormone (e.g. Methoxy polyethylene glycol-epoetin beta, CHEMBL1201829). The collective term for these substances is erythropoiesis-stimulating agent (ESAs). Like endogenous erythropoetin, ESAs exert their effect through binding of the erythropeotin receptor (EpoR, Uniprot P19235) and subsequent activation of the JAK2 (Uniprot O60674) STAT5A (Uniprot P42229) pathway, which results in increased survival of erythrocyte progenitors.

Peginesatide is an ESA with no sequence homology to erythropoetin. Instead, it is composed of two synthetic 21 amino-acid peptides that are linked through a lysine branched PEG chain, as shown below.

The dimeric peptide has a molecular weight of about 4.9 kDa, and the PEG chain has a molecular weight of approximately 40kDa. Peginasetide is dosed as an acetate salt. The empirical formula of the free base is C2031H3950N62O958S6 and total molecular weight ~45 kDa.

Peginesatide does not induce any cytochrome P450s and according to in-vitro protein-binding studies does not bind serum albumin or lipoproteins. The half-life of Peginesatide following intravenous administration is 25.0 ± 7.6 hours in healthy subjects and 47.9 ± 16.5 hours in dialysis patients. Clearance is 0.5 ± 0.2 mL/ and the mean volume of distribution is 34.9 ± 13.8 mL/kg. Peginesatide is mainly cleared through the urine and a study using radio-labelled Peginesatide indicates that it is not excreted unchanged.

Peginesatide has a black box warning and adverse reactions include increased risk for death, myocardial infarcts, stroke, venous thromboembolism, thrombosis of vascular access and tumor progression or recurrence.

An advantage of Peginesatide over other ESAs is that it can be administered at monthly intervals. Given the adverse reactions, the dosage recommendation is to individualize dosing and give the lowest dose that is sufficient to reduce the need for blood transfusions. 0.04 mg/kg is the recommended dose for probing patient response.

Peginesatide was developed by Affymax and Tekeda Pharmaceuticals and is marketed under the trade name Omontys.

Full prescribing information can be found here.