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Showing posts from June, 2013

New Drug Approvals 2013 - Pt. X - Trametinib (Mekinist®)

ATC code:L01XE15
Wikipedia:TrametinibChEMBL2103875
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 MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKV GELKD…

Paper: The Open Access Malaria Box: A Drug Discovery Catalyst for Neglected Diseases

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 Access Ma…

New Drug Approvals 2013 - Pt. IX - Dabrafenib mesylate (Tafinlar®)

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). Dabrafenib potently inhibits multiple mutant B…

Meeting: Computational Electrostatics for Biological Applications (CEBA)

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