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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.

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

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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