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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.

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

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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