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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.

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

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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