SH-4-54

SH-4-54 is an inhibitor of signal transducer and activator of transcription 3 (STAT3; IC₅₀ = 4.7 μM for STAT3 homodimer DNA binding activity). It selectively inhibits STAT3 homodimer over STAT1 and STAT5 homodimer and STAT3:STAT1 heterodimer DNA binding in EGF-stimulated NIH3T3/hEGFR nuclear extracts containing activated STAT1, STAT3, and STAT5 and decreases STAT3 iNOS, Survivin, and Bcl-2 promoter occupancy in MDA-MB-231 cells. SH-4-54 inhibits growth of glioma, breast, and prostate cancer cell lines that express constitutively active STAT3 (IC₅₀s = 1-7.4, 3.8-4.5, and 5.3-5.8 μM, respectively). In vivo, SH-4-54 (3 mg/kg per day) inhibits tumor growth in the U251MG glioma and MDA-MB-231 breast cancer mouse xenograft models.

4-[[(4-Cyclohexylphenyl)methyl][2-[methyl[(2,3,4,5,6-pentafluorophenyl)sulfonyl]amino]acetyl]amino]benzoic Acid acts as a STAT 3 and STAT5 inhibitor. STAT 3 is unusually active in glioblastoma and plays a crucial role in tumor growth

STAT3: 300 nM (Kd); STAT5: 464 nM (Kd)

[1] PEIBIN YUE. Hydroxamic Acid and Benzoic Acid-Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes In Vitro and In Vivo.[J]. Cancer research, 2016, 76 3: 652-663. DOI: 10.1158/0008-5472.can-14-3558