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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.

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

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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