Abstract 7360: Side-by-side evaluation of STAT3 targeted agents in oncology

Abstract Signal transducer and activator of transcription 3 (STAT3) is a critical transcription factor, which is aberrant activated in hematological malignancies, including acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL), as well as solid tumors of the lung, breast, and others. Yet no selective STAT3 inhibitor has reached the clinic owing to disparate chemical matter, binding sites (SH2, DBD, CCD), and mechanisms (pY705 blockade, dimer disruption, DNA binding inhibition, degradation). We established a standardized integrated analytics platform that directly compares 5-10 chemically diverse STAT3 agents—including covalent SH2 ligands, allosteric DBD antagonists and PROTAC degraders—using harmonized biochemical (FP, TR-FRET etc), biophysical (SPR, SPS etc), and cellular (pSTAT3, reporter gene, HiBiT, proliferation) assays. Family and species selectivity, together with resistance panels, reveal distinct vulnerability windows and mechanism-based liabilities for each modality. The same matrix is screened in combination with JAK, SRC, EGFR, and chemotherapy partners to quantify synergy landscapes; By providing a comprehensive molecular-evaluation platform, the program streamlines hit-to-lead decisions, propels STAT3-directed drug discovery and accelerates the path to the clinic. Citation Format: Xiaolan Su, Yue Zhai, Zhu Meng, Mingying Li, Tanfeng Zhao, Zhaoxia Yin, Qian Wang, Yanan Zhao, Lili Chai, Qiang Xia, Tj (Tiejun) Bing, . Side-by-side evaluation of STAT3 targeted agents in oncology abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7360.