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ProCenDecl SIGNED

Synthesis and validation of chemical Probes for Centrosome Declustering: development of potent and selective anti-cancer agents.

Total Cost €

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EC-Contrib. €

0

Partnership

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 ProCenDecl project word cloud

Explore the words cloud of the ProCenDecl project. It provides you a very rough idea of what is the project "ProCenDecl" about.

organization    accumulate    consequent    investigation    led    completely    tendency    derivative    astrazeneca    series    acquired    extra    advantage    responsible    conjugation    tankyrase    form    synthesize    ribose    biorthogonal    tnks1    centrosomes    copies    starting    poly    organelles    provides    catastrophe    microtubules    declustering    aberrant    proteomics    spindles    mitotic    family    library    seems    tools    sar    mechanism    inhibitor    tumor    exploited    spindle    discovery    potently    extensive    normal    orally    cells    cancer    daughter    polimerase    bipolar    parps    16    az0108    clustering    ligation    reports    inhibitors    parp    selective    action    adp    az9482    first    uneven    cell    employed    potent    division    compound    mode    anti    inhibit    point    technologies    contrary    druggability    enzyme    multipolar    centrosome    polymerase    segregation    leads    prevention    chemical    drugs    chromosomes    survival    ribosylation    photoaffinity    pseudo    specificity    phtalazinone   

Project "ProCenDecl" data sheet

The following table provides information about the project.

Coordinator
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE 

Organization address
address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ
website: http://www.imperial.ac.uk/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE UK (LONDON) coordinator 183˙454.00

Map

 Project objective

Cancer cells have the tendency to accumulate extra copies of centrosomes, organelles responsible for the microtubules' organization during cell division. In normal cells, an aberrant number of centrosomes leads to the formation of multipolar spindles, uneven segregation of chromosomes between daughter cells and consequent mitotic catastrophe. On the contrary, cancer cells are able to form a pseudo-bipolar mitotic spindle by a process called centrosome clustering, which provides survival advantage for tumor cells. The specificity of this process can be exploited as a potential novel target for the development of highly selective anti-cancer drugs. The mechanism of centrosome clustering is not completely understood. Particularly, from recent reports it seems that ADP ribosylation factors tankyrase (TNKS1) and ADP-ribose polimerase 16 (PARP-16) have a significant role in the prevention of multipolar spindle formation. Based on these findings and the already druggability of poly (ADP-ribose) polymerase (PARP) enzyme family, a SAR study on phtalazinone PARP inhibitors from AstraZeneca's compound library was carried out. This study led to the discovery of AZ9482, a potent inhibitor of centrosome clustering, and AZ0108 an orally available derivative that is able to potently inhibit PARPs 1/2/6. AZ9482 as well as AZ0108 can be used as a starting point to design and synthesize a first series of chemical proteomics tools, that will allow an extensive investigation of the centrosome declustering mechanism. All currently available technologies in the field of target discovery will be employed, including photoaffinity ligation and biorthogonal conjugation. The acquired knowledge can be used to design novel highly specific and potent anti-cancer drugs that inhibit centrosome clustering with a specific mode of action.

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The information about "PROCENDECL" are provided by the European Opendata Portal: CORDIS opendata.

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