Identification of novel small molecule inhibitors of ETS transcription factors

Abdalla, S.; Forghany, Z.; Ma, J.; Hollander, J.G.; Nachane, R.; Szuhai, K.; ... ; Baker, D.A. (2025)

Article / Letter to editor

The evolutionarily conserved E-Twenty-Six (ETS) family of transcription factors acts downstream of major signal transduction pathways and plays a pivotal role in tissue development and maintenance. Importantly, their function is frequently corrupted in a substantial proportion of tumour types, and they are also indispensable for angiogenic sprouting, a hallmark of cancer, which is essential for fuelling tumour enlargement and dissemination. Consequently, targeting aberrant ETS activity could potentially represent a precise and effective means by which to block tumour growth. Here, we present proof-of-principle high-throughput screens and an initial characterization of candidate hits, as a methodological and conceptual framework for the identification of novel ETS transcription factor inhibitors, which may ultimately lead to new therapeutic avenues for treating cancer.

• angiogenesis
• cancer
• drug development
• ETS transcription factor

• All authors: Abdalla, S.; Forghany, Z.; Ma, J.; Hollander, J.G.; Nachane, R.; Szuhai, K.; Hogendoorn, P.C.W.; Dijke, P. ten; Shah, D.P.; Baker, D.A.
• Date: 2025-04-11
• Journal: FEBS Letters
• Volume: 599
• Issue: 12
• Pages: 1733 - 1748
• DOI: doi:10.1002/1873-3468.70040