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Design and biological characterization of glioblastoma-effective senotherapeutics acting through Michael addition

Public support

  • Provider

    Czech Science Foundation

  • Programme

    Standard projects

  • Call for proposals

    SGA0202600001

  • Main participants

    Ústav molekulární genetiky AV ČR, v. v. i.

  • Contest type

    VS - Public tender

  • Contract ID

    26-21040S

Alternative language

  • Project name in Czech

    Design and biological characterization of glioblastoma-effective senotherapeutics acting through Michael addition

  • Annotation in Czech

    The presence of senescent cells in glioblastoma (GB) is an adverse prognostic marker. Adjuvant senolytic therapy is one of the new, intensively investigated approaches for cancer treatment. In our previous work, we prepared and characterized a new compound, methoxybenzylaminobenzothiophene dioxide (K2071), which exhibits STAT3 inhibitory, antimitotic, anti-migratory, anti-invasive, and senotherapeutic properties. We hypothesize that the mechanism of action of K2071 involves covalent binding to an as-yet unidentified molecular target(s) via a thia-Michael addition. Our pilot findings suggest that further derivatization of K2071 can separate its antimitotic and senotherapeutic effects. In this proposal, we aim to develop novel GB-effective K2071 derivatives with enhanced senolytic and senomorphic properties. Using 2D and 3D in vitro culture models of human GB cell lines, we intend to elucidate their mechanisms of action, potential resistance, and synergies with other senolytics.

Scientific branches

  • R&D category

    ZV - Basic research

  • OECD FORD - main branch

    30204 - Oncology

  • OECD FORD - secondary branch

    30107 - Medicinal chemistry

  • OECD FORD - another secondary branch

    30104 - Pharmacology and pharmacy

  • CEP - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)

    FD - Oncology and haematology<br>FP - Other medical fields<br>FR - Pharmacology and apothecary chemistry

Solution timeline

  • Realization period - beginning

    Jan 1, 2026

  • Realization period - end

    Dec 31, 2028

  • Project status

    Z - Beginning multi-year project

  • Latest support payment

Data delivery to CEP

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

  • Data delivery code

    CEP26-GA0-GA-R

  • Data delivery date

    May 26, 2026

Finance

  • Total approved costs

    12,633 thou. CZK

  • Public financial support

    12,633 thou. CZK

  • Other public sources

    0 thou. CZK

  • Non public and foreign sources

    0 thou. CZK