Small molecule targeting FOXM1 DNA binding domain exhibits anti-tumor activity in ovarian cancer.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
09 Jun 2022
09 Jun 2022
Historique:
received:
08
11
2021
accepted:
26
05
2022
revised:
23
05
2022
entrez:
10
6
2022
pubmed:
11
6
2022
medline:
11
6
2022
Statut:
epublish
Résumé
FOXM1 is a potent oncogenic transcription factor essential for cancer initiation, progression, and drug resistance. FOXM1 regulatory network is a major predictor of adverse outcomes in various human cancers. Inhibition of FOXM1 transcription factor function is a potential strategy in cancer treatment. In this study, we performed structure-based in silico screening to discover small molecules targeting the FOXM1 DNA-binding domain (DBD). Compound XST-20 was identified to effectively suppress FOXM1 transcriptional activities and inhibit ovarian cancer cell proliferation. XST-20 directly interacts with the FOXM1 DNA-binding domain determined by SPR assay. Furthermore, XST-20 was found to significantly reduce the colony-forming efficiency and induce cell cycle arrest and apoptosis. Our study provides a lead compound of FOXM1 inhibitor which may serve as a potential targeted therapy agent for ovarian cancer.
Identifiants
pubmed: 35680842
doi: 10.1038/s41420-022-01070-w
pii: 10.1038/s41420-022-01070-w
pmc: PMC9184618
doi:
Types de publication
Journal Article
Langues
eng
Pagination
280Informations de copyright
© 2022. The Author(s).
Références
Eur J Med Chem. 2014 Jun 23;81:277-88
pubmed: 24852275
Cancer Lett. 2013 Oct 28;340(1):104-12
pubmed: 23856032
Adv Cancer Res. 2013;119:191-419
pubmed: 23870513
Cancer Res. 2008 Nov 1;68(21):8733-42
pubmed: 18974115
Nat Med. 2015 Aug;21(8):938-945
pubmed: 26193342
Nucleic Acids Res. 2017 Jun 2;45(10):5797-5817
pubmed: 28369544
Cell Death Dis. 2018 May 11;9(5):562
pubmed: 29752436
Oncogene. 2017 Jun 15;36(24):3428-3440
pubmed: 28114286
Cancer Res. 2017 Jun 15;77(12):3135-3139
pubmed: 28584182
Oncogene. 2017 Mar;36(10):1404-1416
pubmed: 27593933
Biosci Biotechnol Biochem. 2012;76(12):2360-3
pubmed: 23221713
Cell Chem Biol. 2017 Mar 16;24(3):346-359
pubmed: 28163017
Mol Carcinog. 2019 Oct;58(10):1770-1782
pubmed: 31219654
J Transl Med. 2014 May 20;12:134
pubmed: 24885308
Mol Med Rep. 2017 Oct;16(4):5181-5188
pubmed: 28849004
Exp Cell Res. 2020 Oct 15;395(2):112212
pubmed: 32771525
Lancet. 2019 Mar 23;393(10177):1240-1253
pubmed: 30910306
Elife. 2019 Dec 04;8:
pubmed: 31789593
Int J Mol Sci. 2016 Mar 04;17(3):340
pubmed: 26959013
PLoS One. 2014 May 13;9(5):e96989
pubmed: 24824601
Sci Rep. 2017 Mar 30;7:45377
pubmed: 28358012
CA Cancer J Clin. 2019 Sep;69(5):363-385
pubmed: 31184787
Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4700-5
pubmed: 15781862
Nucleic Acids Res. 2010 Jul;38(13):4527-38
pubmed: 20360045
Oncogene. 2016 Feb 11;35(6):783-92
pubmed: 26073084
Nat Commun. 2014 Nov 12;5:5165
pubmed: 25387393
FEBS Lett. 2014 Aug 25;588(17):3170-9
pubmed: 24999187