Modulating FOXO3 transcriptional activity by small, DBD-binding molecules
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00518629" target="_blank" >RIV/67985823:_____/19:00518629 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/19:10402417
Result on the web
<a href="https://elifesciences.org/articles/48876" target="_blank" >https://elifesciences.org/articles/48876</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.7554/eLife.48876" target="_blank" >10.7554/eLife.48876</a>
Alternative languages
Result language
angličtina
Original language name
Modulating FOXO3 transcriptional activity by small, DBD-binding molecules
Original language description
FOXO transcription factors are critical regulators of cell homeostasis and steer cell death, differentiation and longevity in mammalian cells. By combined pharmacophore-modeling-based in silico and fluorescence polarization-based screening we identified small molecules that physically interact with the DNA-binding domain (DBD) of FOXO3 and modulate the FOXO3 transcriptional program in human cells. The mode of interaction between compounds and the FOXO3-DBD was assessed via NMR spectroscopy and docking studies. We demonstrate that compounds S9 and its oxalate salt S9OX interfere with FOXO3 target promoter binding, gene transcription and modulate the physiologic program activated by FOXO3 in cancer cells. These small molecules prove the druggability of the FOXO-DBD and provide a structural basis for modulating these important homeostasis regulators in normal and malignant cells.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GF17-33854L" target="_blank" >GF17-33854L: Inhibition of FOXO3-DNA interaction by small molecule inhibitors</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
eLife
ISSN
2050-084X
e-ISSN
—
Volume of the periodical
8
Issue of the periodical within the volume
Dec 4
Country of publishing house
GB - UNITED KINGDOM
Number of pages
21
Pages from-to
e48876
UT code for WoS article
000503449700001
EID of the result in the Scopus database
2-s2.0-85076876862