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DUALITY TERMINATED

An Integrated Computational and Experimental Approach to Rapid Synthesis of Highly Selective Dual-Targeted HDAC/CK2, MMP2/CK2 Inhibitors

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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0

 DUALITY project word cloud

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

proliferative    create    interesting    acetyl    ck2    active    therapies    directed    hdac1    environment    matrix    chromatin    progression    family    multiple    synthesize    alternative    treatment    extensive    regulates    dual    drug    inhibition    threonine    computational    interfering    genetic    deacetylation    tumor    constitutively    aberrant    anticancer    single    anti    mmps    group    diseases    mechanisms    apoptotic    resistance    mmp2    dependent    constitutes    selectivity    deacetylases    synthesis    networks    standard    crosstalks    reverse    traditional    inhibitors    metalloproteinases    viability    epigenetic    zn    transcription    repression    difficulties    expression    acetylation    cancer    remove    serine    histones    strategy    prevent    gene    signaling    cocktails    maintenance    groups    serious    modulators    hdacs    kinase    matrixins    fragment    agents    disease    histone    enzymes    condensation    favorable    inducing    chosen    cellular    cell    seek    techniques   

Project "DUALITY" data sheet

The following table provides information about the project.

Coordinator
FUNDACION UNIVERSITARIA SAN PABLO-CEU 

Organization address
address: C ISAAC PERAL 58
city: MADRID
postcode: 28040
website: www.ceu.es

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 Spain [ES]
 Total cost 170˙121 €
 EC max contribution 170˙121 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-04-10   to  2020-04-09

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACION UNIVERSITARIA SAN PABLO-CEU ES (MADRID) coordinator 170˙121.00

Map

 Project objective

Traditional drug design strategy based on a single target has serious difficulties in developing new therapies for diseases such as cancer. Cancer is a very complex multi-genetic disease that involves multiple crosstalks between signaling networks. The use of cocktails of various anticancer agents interfering with different mechanisms has been the standard treatment to prevent the problems of resistance. An alternative approach is to design multi-target modulators, directed to different disease mechanisms. That is the approach we have chosen for this project, where we seek to design, synthesize and evaluate new dual agents based on the inhibition of three enzymes involved in the development and progression of tumor processes: HDAC1, CK2 and MMP2. CK2 is a serine / threonine kinase that is constitutively active and essential for cell viability. Its proliferative and anti-apoptotic properties create a favorable cellular environment for tumor progression and maintenance and, therefore, constitutes an interesting target for the treatment of cancer. Acetylation/deacetylation of histones is one of the epigenetic mechanisms that regulates gene expression. HDACs (histone deacetylases) remove acetyl groups from histones, inducing condensation of chromatin and, therefore, the repression of gene transcription. For this reason, they are considered key targets to reverse aberrant epigenetic changes associated with cancer. Matrix metalloproteinases (MMPs), also called matrixins are another family of Zn-dependent enzymes. Our research group has extensive experience in the design and synthesis of inhibitors of MMP2 provided with high activity and, more importantly, high selectivity over other metalloproteinases. The design of multi-target modulators will be carried out making use of computational techniques and based on the previous experience of the group in the design and synthesis of inhibitors of these three targets through a fragment based process.

 Publications

year authors and title journal last update
List of publications.
2019 Rangasamy, Geronimo, Ortín, Coderch, Zapico, Ramos, de Pascual-Teresa
Molecular Imaging Probes Based on Matrix Metalloproteinase Inhibitors (MMPIs)
published pages: 2982, ISSN: 1420-3049, DOI: 10.3390/molecules24162982
Molecules 24/16 2020-03-06

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