Stafiba: A STAT5‐Selective Small‐Molecule Inhibitor

The transcription factors STAT5a and STAT5b are constitutively active in many human tumors. Combined inhibition of both STAT5 proteins is a valuable approach with promising applications in tumor biology. We recently reported resorcinol bisphosphate as a moderately active inhibitor of the protein‐protein interaction domains, the SH2 domains, of both STAT5a and STAT5b. Here, we describe the development of resorcinol bisphosphate to Stafiba, a phosphatase‐stable inhibitor of STAT5a and STAT5b with activity in the low micromolar concentration range. Our data provide insights into the structure‐activity relationships of resorcinol bisphosphates and the corresponding bisphosphonates for use as inhibitors of both STAT5a and STAT5b.