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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.

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

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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