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Showing posts from March, 2014

Event: Seminar on Allosteric Drug Design, April 2014

On April 30th 2014 the University of Strathclyde will host a seminar on Allosteric Drug Design organised by the smsdrug.net collaboration. The goal of the seminar is to bring together academic and industrial researchers with an interest in allosteric drug design and development with a view to identifying future collaborative and funding opportunities.

The seminar consists of a series of three talks by : Dr. Gerard JP van Westen (EMBL-EBI ; ChEMBL), Prof. Dr. Leonardo Scapozza (University of Geneva) and Dr. Laurent Galibert (Alpine Institute for Drug Discovery). The talks will cover various of drug design in relation to allosteric drug targets. Talks are aimed at a broad audience.

To register and for further information please go to www.engage.strath.ac.uk/event/125/

New Drug Approvals 2014 - Pt. III - Droxidopa (Northera ™)

ATC Code: Unavailable Wikipedia:Droxidopa ChEMBL: CHEMBL2103827
On February 18th the FDA approved Droxidopa (tarde name Northera™) for the treatment of neurogenic orthostatic hypotension (NOH). NOH is a rare, chronic and often debilitating drop in blood pressure upon standing, and is associated with Parkinson's disease, multiple-system atrophy, and pure autonomic failure. Symptoms of NOH include dizziness, light-headedness, blurred vision, fatigue and fainting when a person stands. 
Target(s)
Droxidopa (also known as L-DOPS, L-threo-dihydroxyphenylserine, and SM-5688) is a prodrug which can be converted to norepinephrine (noradrenaline) by Aromatic L-amino acid decarboxylase (Uniprot P20711 ; EC 4.1.1.28). Norepinephrine in turn can be converted to epinephrine by Phenylethanolamine N-methyltransferase ( Uniprot P11086 ). Droxidopa can cross the blood brain barrier, contrary to epinephrine and norepinephrine.  Patients with NOH suffer from depleted levels of epinephrine and norepineph…

New Drug Approvals 2013 - Pt. XXX - Umeclidinium bromide and Vilanterol (Anoro Ellipta™)

ATC codeR03AL03 WikipediaUmeclidinium bromide (and vilanterol)
ChEMBLCHEMBL1187833 (and CHEMBL1198857)
On December 18, 2013, the FDA approved Anoro Ellipta for the once-daily, long-term maintenance treatment of airflow obstruction in patients with obstructive pulmonary disease (COPD). Anoro is a combination of umeclidinium (62.5 mcg - more details below) and vilanterol inhalation powder (25 mcg - already approved in a different formulation). Ellipta is the single inhaler device:



The majority of COPD cases are due to cigarette smoking and this lung disease is a leading cause of death in the United States. Patients affected by COPD experience breathing difficulties worsening with the time as well as chronic cough and chest tightness.


Umeclidinium
Umeclidinium (also known as umeclidinium bromide, GSK573719A and GSK573719) is a small molecule with a molecular weight of 428.6 Da and AlogP of 3.34, 8 rotatable bounds and no Lipinski's rule of five violation.

Molecular formula: C29H34…

New Drug Approvals 2014 - Pt. I Elosulfase Alfa (Vimizim™)

ATC code: A16AB12 ChEMBL:CHEMBL2108676
On February 14, 2014, the FDA approved elosulfase alfa for the treatment of Mucopolysaccharidosis Type IVA (Morquio A syndrome). Elosulfase alfa is intended to replace the missing GALNS enzyme involved in an important metabolic pathway. Absence of this enzyme leads to problems with bone development, growth and mobility.

Mucopolysaccharidoses comprise a group of lysosomal storage disorders caused by the deficiency of
specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAG). Mucopolysaccharidosis IVA (MPS IVA, Morquio A Syndrome) is characterized by the absence or marked reduction in N-acetylgalactosamine-6-sulfatase activity. The sulfatase activity deficiency resultsin the accumulation of the GAG substrates, KS and C6S, in the lysosomal compartment of cells throughout the body. The accumulation leads to widespread cellular, tissue, and organ dysfunction. It is a rare autosomal recessive disease, affecting approximately 8…

New Drug Approvals 2014 - Pt. II - Tasimelteon (HetliozTM)

ATC Code:N05CH
Wikipedia:Tasimelteon

On January 31st 2014, the FDA approved Tasimelteon (Tradename: Hetlioz; Research Code(s): VEC-162, BMS-214778), a melatonin receptor agonist, for the treatment of Non-24-hour sleep-wake disorder (Non-24).
Non-24-hour sleep–wake disorder (Non-24) is a chronic circadian rhythm sleep disorder, mostly affecting blind people. It is characterised by insomnia or excessive sleepiness related to abnormal synchronization between the 24-hour light–dark cycle and the endogenous circadian cycle (slightly longer than 24 hours). This deviation can be corrected by exposure to solar light, which resets the internal clock, however, the loss of photic input, and the absence of light perception in the majority of patients, prevents them from drifting back into normal alignment.
Tasimelteon is an agonist at melatonin MT1 and MT2 receptors, with a relative greater affinity for MT2. These receptors are thought to be involved in the control of circadian rhythms, consequen…

Paper: The ChEMBL database: a taster for medicinal chemists

We have just had this editorial published in Future Medicinal Chemistry. It is a high-level overview of ChEMBL, SureChEMBL and related resources, aimed primarily at medicinal chemists. The Open Access paper is here.
%T The ChEMBL database: a taster for medicinal chemists %J Future Medicinal Chemistry %D 2014 %O DOI:10.4155/fmc.14.8 %A G. Papadatos %A J.P. Overington

Webinar on Drug Targets - 27th March 2014

I'm giving a webinar on Drug Targets and Drug Targeting at 2-3 pm EDT on Thursday March 27th 2014. Please note that Europe and the US have not aligned their saving times then, so the time difference will be 4 hours for the UK and Portugal (6pm GMT/WET), and 5 hours for the most of the rest of western/central Europe (7pm CET) and 6 hours for Finland and Eastern Europe (8pm EET). I plan to cover quite a lot of ground, with quite a lot of new stuff and analyses.
Registration is free on this link http://acswebinars.org/drug-discovery, and the slides will be available after the meeting on this site too. Well done ACS!!
The next in the series, on lead discovery on Thursday 24th April, is by our great friend and collaborator Tudor Oprea, so put that in your diary too.
jpo

Unpacking a GPU computation server...Leviathan unleashed

What / why?
As you might know, EMBL-EBI has a very powerful cluster. Yet some time ago we were running into some limitations and were pondering on how great it would be if we had the ability to run more concurrent threads in a single machine (avoiding the bottleneck that inevitably appears on the network for some jobs).

It turns out there is an answer, namely in the form of a GPU (graphics processing unit). This is the same type of chip that creates 3D graphics for games in your home PC / laptop. While the capabilities of individual calculation cores are relatively limited on GPUs compared to CPUs, they can have a massive amount of them in order to generate 3D environments at the speeds of 60 frames per second. Schematically it looks like this (CPU left, GPU right):


As you can see, the CPU can handle 8 threads concurrently, whereas the GPU can handle 2880 (see also this great youtube video by the myth busters). We have all kinds of ideas of calculations we want to run on the GPUs (tha…