Targeting STAT3 anti-apoptosis pathways with organic and hybrid organic–inorganic inhibitors

Acute Myeloid Leukemia (AML) is a devastating malignancy. Recurrence and drug resistance are major challenges that spur efforts to identify new clinical targets and active agents. STAT3 has emerged as a potential target in resistant types of AML. The naphthalene sulfonamide inhibitor class exhibits efficient anti-STAT3 activity, and targets a newly identified coiled-coil binding site on STAT3. Although it is well established as a potential target, inhibiting STAT3 function has proven challenging. This paper describes two different approaches to inhibitor design, based on both traditional small molecules and also hybrid inorganic–organic inhibitors based on rhodium(II)–drug conjugates.