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TiDrugArchitectures SIGNED

Highly Competent and Safe Titanium(IV) Therapeutic Frameworks that are Cancer Targeted based on Complex 1, 2, and 3D Chemical Architectures

Total Cost €

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EC-Contrib. €

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Partnership

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 TiDrugArchitectures project word cloud

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

custom    water    phenolato    dependent    complexes    geometries    possibly    enhanced    moieties    compound    linear    bulk    conjugates    biochemistry    biocompatible    designed    hydrophilicity    drugs    cellular    therapeutic    bonds    synergistic    sensitive    entities    directions    bio    anticancer    shown    analyzing    centers    options    polymeric    constructed    tumor    rigid    penetration    3d    tiiv    tshuva    chemical    steroid    biological    permeability    incorporating    multiple    combine    cages    steric    hormone    sites    agents    safe    species    stability    derivatives    selective    cancer    types    superior    selectively    yield    direct    metal    release    ph    accessibility    customized    unlimited    linked    small    group    stable    molecules    mystery    vitro    pt    dissociation    active    bioactive    markedly    unraveling    transport    optimal    dendritic    action    assemblies    penetrating    selectivity    donors    desired    flexible    maintaining    frameworks    cells    redox    vivo    medicinal    binding    conjugate    cell    combination    mechanism    peptides    interaction   

Project "TiDrugArchitectures" data sheet

The following table provides information about the project.

Coordinator
THE HEBREW UNIVERSITY OF JERUSALEM 

Organization address
address: EDMOND J SAFRA CAMPUS GIVAT RAM
city: JERUSALEM
postcode: 91904
website: www.huji.ac.il

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 Israel [IL]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-06-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE HEBREW UNIVERSITY OF JERUSALEM IL (JERUSALEM) coordinator 2˙000˙000.00

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 Project objective

This proposal aims to develop custom designed anticancer therapeutic frameworks that are effective, stable, safe, and tumor targeted, based on the biocompatible TiIV metal. The Tshuva group has established that water stable phenolato TiIV complexes are especially effective as anticancer agents both in vitro and in vivo, with markedly reduced side effects. Optimal derivatives will be developed to combine activity, stability, and biological accessibility, by maintaining small steric bulk while incorporating strong binding donors and hydrophilicity. The mechanism of action will be investigated by chemical and biological methods, including analyzing bio-distribution, cellular pathways and targets, and interaction with bio-molecules. Specifically, the active metal centers will be linked to bioactive moieties through redox-sensitive S–S bonds to enable tumor targeting. Cell penetrating peptides will facilitate cellular penetration for redox-dependent release of the active species selectively in cancer cells; steroid moieties will direct selectivity to hormone-dependent cancer cell types. Since the combination of TiIV- with Pt-based drugs has shown synergistic effects, multi-active entities will include two or more metal centers, possibly also linked to a transport unit. In addition to linear conjugates, polymeric and dendritic assemblies, exploiting the enhanced permeability of cancer cells, will be constructed with theoretically unlimited options for targeted delivery of multiple active sites. Most importantly, flexible well-defined redox-sensitive cages, as well as rigid pH sensitive complex cages, constructed with customized 3D geometries, will enable specific targeting of any active compound or conjugate and selective dissociation only where desired. This study should yield superior anticancer drugs, while unraveling the mystery of their complex biochemistry, and will contribute to the development of novel chemical and medicinal research directions and applications.

 Publications

year authors and title journal last update
List of publications.
2018 Maya Miller, Edit Y. Tshuva
Racemic vs. enantiopure inert Ti( iv ) complex of a single diaminotetrakis(phenolato) ligand in anticancer activity toward human drug-sensitive and -resistant cancer cell lines
published pages: 39731-39734, ISSN: 2046-2069, DOI: 10.1039/c8ra08925f
RSC Advances 8/69 2019-08-29
2018 Avia Tzubery, Naomi Melamed-Book, Edit Y. Tshuva
Fluorescent antitumor titanium( iv ) salen complexes for cell imaging
published pages: 3669-3673, ISSN: 1477-9226, DOI: 10.1039/c7dt04828a
Dalton Transactions 47/11 2019-05-10

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