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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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 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.

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

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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