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Discovery of new inhibitors of nuclease MRE11

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F25%3A00617707" target="_blank" >RIV/68378050:_____/25:00617707 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216224:14310/25:00140679 RIV/00159816:_____/25:00082273

  • Result on the web

    <a href="https://doi.org/10.1016/j.ejmech.2024.117226" target="_blank" >https://doi.org/10.1016/j.ejmech.2024.117226</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.ejmech.2024.117226" target="_blank" >10.1016/j.ejmech.2024.117226</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Discovery of new inhibitors of nuclease MRE11

  • Original language description

    MRE11 nuclease is a central player in signaling and processing DNA damage, and in resolving stalled replication forks. Here, we describe the identification and characterization of new MRE11 inhibitors MU147 and MU1409. Both compounds inhibit MRE11 nuclease more specifically and effectively than the relatively weak state-of-theart inhibitor mirin. They also abrogate double-strand break repair mechanisms that rely on MRE11 nuclease activity, without impairing ATM activation. Inhibition of MRE11 also impairs nascent strand degradation of stalled replication forks and selectively affects BRCA2-deficient cells. Herein, we illustrate that our newly discovered compounds MU147 and MU1409 can be used as chemical probes to further explore the biological role of MRE11 and support the potential clinical relevance of pharmacological inhibition of this nuclease.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2025

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    European Journal of Medicinal Chemistry

  • ISSN

    0223-5234

  • e-ISSN

    1768-3254

  • Volume of the periodical

    285

  • Issue of the periodical within the volume

    5 March

  • Country of publishing house

    FR - FRANCE

  • Number of pages

    20

  • Pages from-to

    117226

  • UT code for WoS article

    001410134300001

  • EID of the result in the Scopus database

    2-s2.0-85214325739