The ChEMBL-og

ATC code: L01XE15 Wikipedia: Trametinib ChEMBL2103875 On May 29th 2013, the FDA approved trametinib (Mekinist®) for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, and who have not received prior BRAF inhibitor treatment. Trametinib inhibits mutant BRAF signalling through the inhibition of a downstream kinase, MEK. In clinical trials trametinib improved the progression-free survival (PFS) from 1.5 months on standard of care chemotherapy to 4.8 months on trametinib. Trametinib is the first approved targeted MEK inhibitor. It inhibits the kinase catalytic activity of its targets, mitogen-activated extracellular signal regulated kinase 1 and 2 ( MAP2K1 AKA MEK1, Uniprot: Q02750 ) and MAP2K2 AKA MEK2, Uniprot: P36507 ). The sequences of the targets are here: >sp|Q02750|MP2K1_HUMAN Dual specificity mitogen-activated protein kinase kinase 1 OS=Homo sapiens GN=MAP2K1 PE=1 SV=2 MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEE...

Historically, one of the key problems in neglected disease drug discovery has been identifying new and interesting chemotypes. Phenotypic screening of the malaria parasite, Plasmodium falciparum has yielded almost 30,000 submicromolar hits in recent years. To make this collection more accessible, a collection of 400 chemotypes has been assembled, termed the Malaria Box. Half of these compounds were selected based on their drug-like properties and the others as molecular probes. These can now be requested as a pharmacological test set by malaria biologists, but importantly by groups working on related parasites, as part of a program to make both data and compounds readily available. In this paper, the analysis and selection methodology and characteristics of the compounds are described. Data from studies involving the Malaria Box will be in ChEMBL and the ChEMBL Malaria portal. %A T. Spangenberg %A J.N. Burrows %A P. Kowalczyk %A S. McDonald %A TNC Wells %D 2013 %T The Open Ac...

ATC code: L01XE15 Wikipedia: Dabrafenib On May 29th 2013 the FDA approved dabrafenib mesylate (trade name: Tafinlar®, research codes GSK-2118436A and GSK-2118436B) for the treatment of patients with unresectable metastatic melanoma harbouring the BRAF V600E mutation. In clinical trials, dabrafenib showed improved progression-free survival (PFS) over the comparator dacarbazine (median PFS 5.1 months for dabrafenib compared to 2.7 months for dacarbazine). Moreover, in a multicentre open-label Phase II trial dabrafenib showed effectiveness on brain metastases of melanoma regardless of whether the patients had been previously treated. As with the previously approved BRAF inhibitor, vemurafenib, the major side effect of dabrafenib is the emergence of malignant cutaneous squamous cell carcinomas and keratoacanthomas. The main molecular target for dabrafenib is the human mutant serine/threonine kinase, BRAF (Uniprot for wild type protein: P15056 ). ...

Computational Electrostatics for Biological Applications ( CEBA) is an international meeting joining researchers in computational disciplines aiming at discussing and exploring different approaches to improve the electrostatics calculations in the Molecular Biology field. The scope of the meeting is quite broad. However, a special focus on theoretical, numerical and modeling aspects of the Poisson-Boltzmann equation and its applications to the NanoBiotechnology field will be given. The conference website is here

The joy in submitting a PhD is insurmountable, and some say it feels like going to heaven ( n.b. Ben!). Anyway, four EMBL-EBI faculty are recruiting PhD students in this round of the EMBL International PhD Programme.  The deadline for submissions is 17th June 2013 - so not long away now - get your skates on if you are interested. These four year studentships will be available from October 2013 onwards. The labs taking students this round are: Alex Bateman's group . John Overington's group . Chris Steinbeck's group . Sarah Teichmann's group . Click on the links above to see current group research interests. There are also other excellent PhD studentship opportunities available at EMBL in Heidelberg and various of the other EMBL Outstations - for details see here . jpo

ATC Code: R03AK10 Wikipedia: Vilanterol On May 10 th , the FDA approved Vilanterol (Tradename: Breo Ellipta ; Research Code: GW-642444M), a long-acting beta 2 -adrenergic agonist , in combination with the already approved fluticasone furoate , an inhaled corticosteroid , for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD). Chronic obstructive pulmonary disease (COPD) is characterised by the occurrence of chronic bronchitis or emphysema , a pair of commonly co-existing diseases of the lungs in which the airways become narrowed. Bronchial spasms, a sudden constriction of the muscles in the walls of the bronchioles , occur frequently in COPD. Vilanterol is a new long-acting beta 2  receptor agonist that through the activation of the beta 2 adrenergic receptors present in the bronchial smooth muscle, leads to bronchodilation, and consequently eases the symptoms of COPD. The beta 2 adrenergeic re...

If you were looking for an up-to-date review of computational applications of bioisosterism in medicinal chemistry, then look no further. After an overview of the history and evolution of bioisosterism, the paper reports the various attempts aiming to capture and quantify it, as well as to disseminate its examples in the context of modern computer-aided drug discovery. Link to the paper here .  %A G. Papadatos %A N. Brown %T In silico applications of bioisosterism in contemporary medicinal chemistry practice %J WIREs Computational Molecular Science %D 2013 %O doi.10.1002/wcms.1148 George