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

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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