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Showing posts from May, 2014

The results are out!

The results of the Teach-Discover-Treat (TDT) 2014 challenge were out earlier this week. TDT is an initiative to provide high quality computational chemistry tutorials that impact education and drug discovery for neglected diseases with a special focus on freely available software tools and reproducibility. 
We are very happy to announce that Rodrigo Ochoa, former summer intern in the group two years ago, won the second place (KNIME award) at the TDT challenge.

Rodrigo’s entry was based on myChEMBL (Open Innovation track) and contains several KNIME and IPython Notebook tutorials within an NTD computational research setting.   More details here.

PS: Watch this space for an update on myChEMBL very soon. 

Team myChEMBL

Paper: An atlas of genetic influences on human blood metabolites

We got involved in the analysis of a really interesting GWAS/metabolomics study, with a publication just appearing in Nature Genetics. A link to the paper is here.

Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most comprehensive exploration of genetic loci influencing human metabolism thus far, comprising 7,824 adult individuals from 2 European population studies. We report genome-wide significant associations at 145 metabolic loci and their biochemical connectivity with more than 400 metabolites in human blood. We extensively characterize the resulting in vivo blueprint of metabolism in human blood by integrating it with information on gene expression, heritability and overlap with known loci for complex disorders, inborn errors of metabolism and pharmacological targets. We further developed a database and web-based resources for data minin…

Paper: Towards predictive resistance models for agrochemicals by combining chemical and protein similarity via proteochemometric modelling

There's an Open Access opinion paper out in J. Chem. Biol. on the potential application of chemo/bio joint QSAR techniques that have historically been developed and applied to primarily human pharmaceutical applications, to the agrochemical area.

Link to the paper is here.

Later in the summer of 2014, there is some very exciting news on agrochemical data for ChEMBL!

%0 Journal Article %D 2014 %@ 1864-6158 %J Journal of Chemical Biology %R 10.1007/s12154-014-0112-2 %T Towards predictive resistance models for agrochemicals by combining chemical and protein similarity via proteochemometric modelling %U http://dx.doi.org/10.1007/s12154-014-0112-2 %I Springer Berlin Heidelberg %8 2014-05-15 %K Polypharmacology %K Cheminformatics %K Machine learning %K Resistance %A Westen, Gerard J.P. %A Bender, Andreas %A Overington, John P. %P 1-5 %G English

New Drug Approvals 2014 - Pt. VIII - Siltuximab (Sylvant™)

ATC Code:
Wikipedia:Siltuximab
ChEMBL:CHEMBL1743070

On April 23rd 2014 the FDA approved Siltuximab (Sylvant™) for the treatment of patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV-)-negative and human herpes virus-8 (HHV-8)-negative.

Castleman disease (Also known as giant or angiofollicular lymph node hyperplasia, lymphoid hamartoma, or angiofollicular lymph node hyperplasia) is an abnormal non-cancerous growth of the lymph node that can resemble lymphomas. It is contributed to by hyperproliferation of cytokine-producing lymphocytes. Castleman disease can be unicentric (involving a single lymph node) or multicentric (systemic). Siltuximab is approved for the multi centric disease. Overproduction of IL-6 has been linked to systemic manifestations in patients with MCD.

Siltuximab is a chimeric (human and mouse) anti-IL6 antibody. It binds human IL-6 thus preventing the interaction of IL-6 to both soluble and membrane- bound IL-6 receptors.

The…

New Drug Approvals 2014 - Pt. VII - Ramucirumab (Cyramza™)

ATC Code:
Wikipedia:Ramucirumab
ChEMBL:CHEMBL1743062


On April 21, 2014 the FDA approved Ramucirumab (Cyramza™) for the treatment of patients with advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior treatment with fluoropyrimidine- or platinum-containing chemotherapy.

Gastric cancer has a very poor prognosis, with adenocarcinomas constituting ~95% of all gastric cancers (CRUK).

In a randomized, double-blind, multicenter study of ramucirumab plus best supportive care (BSC) compared with placebo plus BSC of 355 patients with locally advanced or metastatic gastric cancer (including adenocarcinoma of the gastro-esophageal junction [GEJ]), ramucirumab improved the overall survival to a median of 5.2 months, compared to 3.8 with the placebo arm. Progression-free survival (PFS) was improved from a median of 1.3 months in the placebo arm to 2.1 months in the ramucirumab arm.

Cyramza has been issued a boxed warning because…

ChEMBL Tour 2014 - The Netherlands, Belgium, and Luxembourg

Last year Louisa Bellis toured the UK to present on SMSdrug.net and ChEMBL. The tour was well received and a large number of people that had not heard of ChEMBL were introduced to ChEMBL.

Following the success of the previous tour, Gerard van Westen (EMBL –EBI) is going to be doing a 2014 ChEMBL tour. This year’s tour will be going to the BeNeLux. For dates and locations see below. Please feel free to attend and meet up / chat on ChEMBL, contactable via email on gerardvw [at] ebi.ac.uk

Current dates are as follows:

19th of May – Maastricht University
Host: Egon Willighagen
Time: 12.00-17.00
ChEMBL + Allosteric modulators

20th of May – Maastricht University
Host: Jos Kleinjans
Time: 09.00 - 11.30
ChEMBL + Advanced ChEMBL

20th of May – KU Leuven
Host: Pieter Annaert
Time: 14.00 -17.00
ChEMBL

21th of May – KU Leuven
Host: Piet herdewyn
Time: 09.00 -10.00
ChEMBL

21th of May – University of Luxembourg
Host: Reinhard Schneider
Time: 13.00 - 17.00
ChEMBL + Advanced ChEMBL

22nd of May – Universiteit A…

New Drug Approvals 2014 - Pt. VI - Florbetaben F18 (Neuraceq™)

ATC Code: Unavailable Wikipedia:Florbetaben_F18 ChEMBL: CHEMBL1908906
On March 19th the FDA approved Florbetaben F18 (Neuraceq™) as a radioactive diagnostic agent for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid (βA) neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease or other causes of cognitive decline.

Alzheimer's disease is the most common form of dementia, can currently not be cured and is characterised by a progressive disease pattern that usually leads to death.  Alzheimer's is predicted to affect 1 in 85 people globally by 2050.

Target(s)
Florbetaben binds with high affinity to βA in brain homogenates and selectively labels βA plaques and cerebral amyloid angiopathy. βA (PDB ; Uniprot P05067) denotes 36-43 length peptides that are believed to be crucially involved in the Alzheimer's disease mechanism. βA aggregates in the brain of Alzheimer's patients and is derived fr…

ChEMBL funding 2014-2019.

We have recently heard that our funding application for continuation of the ChEMBL database has been successful, and going forward the resource will be funded by The Wellcome Trust and core-funding from EMBL. Below is the text from the lay description of the application. First though, we must thank you, ChEMBL users, for your support and feedback to all that we do. There is a lot of exciting future data and technology to come, and we'll post more details about what we plan to do in future blog posts. As always, we are always happy to receive visitors for tea and cake!

Drug Discovery is costly, slow and complex, and despite much fundamental scientific progress, the translation of this into new safer medicines has been slower than anticipated. One of the key steps in drug discovery is the identification of specific drug-like bioactive compounds that modulate a gene believed to be causal in the treatment of a disease. Most new drugs are themselves chemically similar to old drugs, bu…

New Drug Approvals 2014 - Pt. V - Metreleptin (MyaleptTM)

ATC Code (s):A08A, A10X, A16A
Wikipedia:Metreleptin

On February 24th 2014, the FDA approved metreleptin (Tradename: Myalept), a leptin analogue, as an adjunct to diet and replacement therapy, for the treatment of complications associated with leptin deficiency in patients with congenital or acquired generalized lipodystrophy.
Lipodystrophy is a rare condition characterized by abnormalities in adipose (fat) tissue distribution. It can be congenital, i.e. the patient is born with little or no adipose tissue, or it can be acquired, for example, after prolonged antiretroviral drug therapy some patients keep on losing adipose tissue with time. The deficiency of adipose tissue leads to hypertriglyceridemia and ectopic deposition of fat in non-adipose tissues such as liver and muscle, contributing to metabolic abnormalities including insulin resistance.

Leptin is an endogenous hormone, predominantly secreted in the adipose tissue, responsible to signal to the central nervous system, the stat…