Work

Stafib‐2‐CR: an Improved Nanomolar and Selective Inhibitor of the Transcription Factor STAT5b Developed by Conformational Restriction of Stafib‐2

Year: 2025

Type: article

Abstract: The highly homologous transcription factors STAT5a and STAT5b are overactivated in many human tumor types. We recently reported catechol bisphosphates as the first chemical entities that inhibit STAT5b with selectivity over STAT5a. Here, we apply conformational restriction strategies to increase the activity and selectivity of Stafib-2, the most potent STAT5b inhibitor reported to date. The best conformationally restricted Stafib-2 analogue 8b (dubbed Stafib-2-CR) displayed approximately threefold higher activity against STAT5b than Stafib-2, associated with higher selectivity over STAT5a. Its cell-permeable prodrug 17 (dubbed Pomstafib-2-CR) inhibits phosphorylation of STAT5b in cultured human leukemia cells with slightly higher activity and selectivity over STAT5a than Pomstafib-2, the prodrug corresponding to Stafib-2.

Source: Chemistry - A European Journal

DOI: 10.1002/chem.202502809

Authors: Theresa Münzel, Angela Berg, Christoph Protzel, Sylvie Schäfer, Alexander Jensen‐Feinhals, Thorsten Berg

Institution: Leipzig University

Language: English

Topic: Cytokine Signaling Pathways and Interactions

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,640