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microRNA FBDD

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Towards microRNA modulators by fragment based drug discovery FBDD approaches

MicroRNAs have been identified as important endogenous regulators of gene function. Aberrant regulation of them has been linked to various human diseases. Small molecule intervention has the potential to provide a new therapeutic... ver más

28/02/2013

THE CHANCELLOR MAS...

200K€

Presupuesto del proyecto: 200K€

Líder del proyecto

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2013-02-28 No tenemos la información de la convocatoria

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Líder del proyecto

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UN... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 200K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto MicroRNAs have been identified as important endogenous regulators of gene function. Aberrant regulation of them has been linked to various human diseases. Small molecule intervention has the potential to provide a new therapeutic strategy. The aim of the project is the identification of selective microRNA modulators by fragment-based drug discovery (FBDD) approaches. MicroRNAs are short ribonucleic acid (RNA) molecules, on average only 22 nucleotides long that act as post-transcriptional regulators by binding to complementary sequences in the three prime untranslated regions (3`UTRs) of target messenger RNA transcripts (mRNAs), usually resulting in efficient sequence-specific gene silencing, which is referred to as RNA interference (RNAi). The numerous reports indicating a role of microRNAs in connection with diseases such as diabetes, neurological disorders, and cancer raises the question whether microRNA could be targeted in the development of a novel therapeutic strategy. Fragment-based drug discovery (FBDD) methods have been developed for finding lead compounds as part of the drug discovery process. The approach is based on identifying small molecules (with a molecular weight less than 250 Da and so called fragments), which generally bind only weakly to the biological target, and then iteratively elaborating them to produce successively more potent compounds. The target microRNA will be microRNA-122, which plays a key role in hepatitis C virus infection, microRNA-155, an inducer of pancreatic cancer by suppressing the expression of cell-cycle protein p53 and let-7 microRNA, which has been shown to control the timing of development of nematode Caenorhabditis elegans from the last larval stage to adulthood. Detailed binding studies will be done by NMR spectroscopy. In conclusion the druggability of microRNA will be proved.

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