Počet záznamů: 1
Lengthening the Guanidine–Aryl Linker of Phenylpyrimidinylguanidines Increases Their Potency as Inhibitors of FOXO3-Induced Gene Transcription
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SYSNO ASEP 0562268 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Lengthening the Guanidine–Aryl Linker of Phenylpyrimidinylguanidines Increases Their Potency as Inhibitors of FOXO3-Induced Gene Transcription Tvůrce(i) Kohoutová, Klára (FGU-C) ORCID
Dočekal, V. (CZ)
Ausserlechner, M. J. (AT)
Kaiser, N. (AT)
Tekel, A. (CZ)
Mandal, R. (CZ)
Horváth, M. (CZ)
Obšilová, Veronika (FGU-C) RID, ORCID, SAI
Veselý, J. (CZ)
Hagenbuchner, J. (AT)
Obšil, Tomáš (FGU-C) RID, ORCIDZdroj.dok. ACS Omega. - : American Chemical Society - ISSN 2470-1343
Roč. 7, č. 38 (2022), s. 34632-34646Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova DNA binding ; forkhead box O 3 ; nuclear magnetic resonance ; neuroblastoma ; chemoresistance ; senescence Obor OECD Biochemistry and molecular biology CEP GA21-02080S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000862940400001 EID SCOPUS 85139331926 DOI 10.1021/acsomega.2c04613 Anotace Increased FOXO3 nuclear localization is involved in neuroblastoma chemoresistance and tumor angiogenesis. Accordingly, FOXO3 inhibition is a promising strategy for boosting antitumor immune responses and suppressing FOXO3-mediated therapy resistance in cancer cells. However, no FOXO3 inhibitors are currently available for clinical use. Nevertheless, we have recently identified (4-propoxy)phenylpyrimidinylguanidine as a FOXO3 inhibitor in cancer cells in the low micromolar range. Here, we report the synthesis and structure–activity relationship study of a small library of its derivatives, some of which inhibit FOXO3-induced gene transcription in cancer cells in a submicromolar range and are thus 1 order of magnitude more potent than their parent compound. By NMR and molecular docking, we showed that these compounds differ in their interactions with the DNA-binding domain of FOXO3. These results may provide a foundation for further optimizing (4-propoxy)phenylpyrimidinylguanidine and developing therapeutics for inhibiting the activity of forkhead box (FOX) transcription factors and their interactions with other binding partners. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2023 Elektronická adresa https://doi.org/10.1021/acsomega.2c04613
Počet záznamů: 1