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GlioVac

Validation of a conceptually new treatment for glioblastoma multiforme with an IP protected small molecule

Total Cost €

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EC-Contrib. €

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Partnership

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 GlioVac project word cloud

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

cellular    synthesis    cancer    significantly    induction    gmp    glp    life    isolated    compounds    brain    vulnerability    patent    oral    plan    karolinska    commercialization    exposure    chemotherapy    multiforme    termed    composition    vivo    reverses    efficacy    diagnosed    mechanism    death    cytotoxicity    small    compare    exhibits    innovation    gbm    unanticipated    cell    institutet    vacuolization    intellectual    leads    disease    complete    previously    vacquinol    structure    potency    glioblastoma    reveals    ab    discovery    nine    cytoplasmic    cells    gscs    protection    human    delicate    massive    favorable    prolongs    dosage    amending    astrocytes    models    toxicological    molecule    vitro    regimen    stereo    membrane    competing    property    selective    preclinical    pharmacokinetics    isomer    innovations    marginal    types    animal    clinical    patients    bioavailability    chemical    synthetic    tumor    validate    appropriate    approximately    excellent    expansion    trials    form    rapid    therapy    aggressive    exquisitely    examined    protect    filed    stage    compatible    optimized    rupture    relationship    expectancy    times    viability    ip    macropinocytosis    survival    reduces   

Project "GlioVac" data sheet

The following table provides information about the project.

Coordinator		 KAROLINSKA INSTITUTET 

Organization address
address: Nobels Vag 5
city: STOCKHOLM
postcode: 17177
website: www.ki.se

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 Sweden [SE]
 Total cost 149˙693 €
 EC max contribution 149˙693 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-PoC
 Funding Scheme ERC-POC
 Starting year 2015
 Duration (year-month-day) from 2015-03-01   to  2016-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KAROLINSKA INSTITUTET SE (STOCKHOLM) coordinator 149˙693.00

Map

 Project objective

Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer with marginal life expectancy even with the most aggressive available therapy. We have identified a previously unanticipated vulnerability of GSCs which when targeted, leads to a rapid and complete cell death of all tumor cells isolated from nine different patients diagnosed with GBM. The cellular mechanism has been identified and involves an increased vulnerability of GSCs to massive vacuolization which can be induced by a small molecule, termed Vacquinol-1. The vacuolization results from an induction of massive macropinocytosis leading to cytoplasmic membrane rupture and cell death. Vacquinol-1 reduces viability in vitro with approximately 70 times greater potency than current chemotherapy and efficiently and significantly reverses disease and prolongs survival in animal models of human GBM. Vacquinol-1 is highly selective for glioblastoma cells and is not present in other examined cell types, including astrocytes from the brain. Vacquinol-1 has favorable pharmacokinetics, oral bioavailability and exhibits excellent overall preclinical characteristics. Synthetic chemical expansion of Vacquinol-1 reveals an exquisitely delicate structure activity relationship. IP protection has been filed. In order to be able to validate this discovery into an innovation and possible commercialization we need to: 1) Compare potency and efficacy with competing compounds in development stage. 2) Establish optimized dosage regimen from in vitro and in vivo cytotoxicity and brain exposure measurements. 3) Develop a GMP-compatible stereo-selective synthesis of an appropriate Vacquinol-1 isomer for amending composition of matter to patent and pre-GLP/GLP toxicological and phase I clinical trials. 4) Together with Karolinska Institutet Innovations AB protect the intellectual property, validate commercialization potential and establish a development plan.

 Publications

year authors and title journal last update
List of publications.
2016 Lars G. J. Hammarström, Robert K. Harmel, Mikael Granath, Rune Ringom, Ylva Gravenfors, Katarina Färnegårdh, Per H. Svensson, David Wennman, Göran Lundin, Ylva Roddis, Satish S. Kitambi, Alexandra Bernlind, Fredrik Lehmann, Patrik Ernfors
The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features
published pages: 8577-8592, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b01009 		Journal of Medicinal Chemistry 59/18 2019-07-22

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