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Target5LO SIGNED

Targeting 5-lipoxygenase in the context of Acute Myeloid Leukemia

Total Cost €

0

EC-Contrib. €

0

Partnership

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 Target5LO project word cloud

Explore the words cloud of the Target5LO project. It provides you a very rough idea of what is the project "Target5LO" about.

medical    models    fast    windows    off    synthetic    implications    cancers    validated    mouse    cleavable    learning    completion    medicinal    expression    release    patients    entities    cornerstone    dosage    discontinued    drugs    pipelines    chemistry    preclinical    polypharmacology    site    lapachone    treat    investigation    il7r    biomarker    displaying    vitro    fda    pernicious    adverse    untargeted    leukemia    broad    biophysical    vivo    antibody    anti    successful    therapeutic    approved    quantitative    chemical    drug    unmet    reactions    cells    disseminated    exploring    spatiotemporal    modulator    yield    allosteric    considering    programs    forms    natural    myeloid    applicability    disease    toxicity    fact    naphthoquinone    linkers    foresee    strategies    showed    lipoxygenase    bioactivity    model    discovery    machine    dozens    accurate    efficacy    aml    hope    leukaemia    imperative    biology    conjugates    profile    narrow    blood    acute    profound    validate    deployment    modulate    lp    overcome    lo    correlated    anticancer    disclosed    constructs    employing    conjugate    sought    clinical   

Project "Target5LO" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE 

Organization address
address: TRINITY LANE THE OLD SCHOOLS
city: CAMBRIDGE
postcode: CB2 1TN
website: www.cam.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 195˙454 €
 EC max contribution 195˙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-CAR
 Starting year 2018
 Duration (year-month-day) from 2018-03-01   to  2020-02-29

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE UK (CAMBRIDGE) coordinator 195˙454.00

Map

 Project objective

Drug efficacy is cornerstone for successful drug discovery programs. Considering that, on average, FDA-approved drugs modulate dozens of off-targets it remains imperative to find strategies to overcome adverse drug reactions correlated with pernicious polypharmacology. In fact, several chemical entities displaying promising anticancer are discontinued from drug development pipelines due to narrow therapeutic windows in pre-clinical models. Here, we propose the development of antibody-drug conjugates exploring the unique bioactivity profile of the naphthoquinone natural product-lapachone (Lp) against acute myeloid leukemia (AML), an unmet medical need. Using a machine learning method, we disclosed Lp as an allosteric modulator of 5-lipoxygenase (5-LO), correlated its anticancer activity with 5-LO expression in blood cancers and showed its efficacy in a disseminated mouse model of AML.

In this project, a comprehensive investigation of novel means for the targeted delivery of Lp to leukaemia cells is sought after, considering both the promising bioactivity profile but also the significant toxicity in untargeted dosage forms. We apply state-of-the-art synthetic medicinal chemistry to design and access cleavable linkers, and site-specifically conjugate Lp to an anti-IL7R antibody, a validated biomarker in AML and other leukaemia’s. We aim at employing biophysical and chemical biology approaches to validate quantitative and fast release of Lp with accurate spatiotemporal control in in vitro disease models. Finally, we will validate the deployment of the constructs through preclinical in vivo models of AML. We foresee broad applicability of the developed technology, which may have profound implications in drug discovery. Upon successful completion of this research program, we hope to yield a new targeted drug to treat AML patients with improved efficacy and reduced side-effects.

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The information about "TARGET5LO" are provided by the European Opendata Portal: CORDIS opendata.

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