The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of Ewing's sarcoma
Open accessAbstract
Many sarcomas and leukemias carry nonrandom chromosomal translocations encoding tumor-specific mutant fusion transcription factors that are essential to their molecular pathogenesis. Ewing's sarcoma family tumors (ESFTs) contain a characteristic t(11;22) translocation leading to expression of the oncogenic fusion protein EWS-FLI1. EWS-FLI1 is a disordered protein that precludes standard structure-based small-molecule inhibitor design. EWS-FLI1 binding to RNA helicase A (RHA) is important for its oncogenic function. We therefore used surface plasmon resonance screening to identify compounds that bind EWS-FLI1 and might block its interaction with RHA. YK-4-279, a derivative of the lead compound from the screen, blocks RHA binding to EWS-FLI1, induces apoptosis in ESFT cells and reduces the growth of ESFT orthotopic xenografts. These findings provide proof of principle that inhibiting the interaction of mutant cancer-specific transcription factors with the normal cellular binding partners required for their oncogenic activity provides a promising strategy for the development of uniquely effective, tumor-specific anticancer agents.
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“To further support YK-4-279 as a functional inhibitor of EWS-FLI1, we transfected COS7 cells with EWS-FLI1 and NR0B1 reporter-luciferase plasmid (containing EWS-FLI1 regulatory GGAA element”
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Molotkova, A., Deniz, E., Swift, M., Glasgow, E., Ma, J., Petro, J. A., Frye, I., Ozdemirli, M., Pesic, D., Ahern, G. P., et al. (2026) · Cancer Research Communications · doi:10.1158/2767-9764.crc-26-0068
Self-citation
Metadata
- Authors
- Erkizan, H. V., Kong, Y., Merchant, M., Schlottmann, S., Barber-Rotenberg, J. S., Yuan, L., Abaan, O. D., Chou, T.-H., Dakshanamurthy, S., Brown, M. L., Üren, A., & Toretsky, J. A.
- Venue
- Nature Medicine
- Published
- 2009-07
- Volume
- 15
- Issue
- 7
- Pages
- 750-756
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2007438323
- Cited by
- 452
- References
- 5
- FWCI
- 20.33
- Type
- journal article
- Language
- en
- Open access
- green
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