SS-4 is a highly selective small molecule inhibitor of STAT3 tyrosine phosphorylation that potently inhibits GBM tumorigenesis in vitro and in vivo.

Yinan Wang¹, Chuanhe Yang¹, Michelle M Sims¹, Joshua R Sacher², Mithun Raje³, Hemantkumar Deokar³, Peibin Yue⁴, James Turkson⁴, John K Buolamwini⁵, Lawrence M Pfeffer⁶

¹Department of Pathology and Laboratory Medicine (College of Medicine), and the Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.

²Cyclica, Inc. 207 Queens Quay West, Suite 420, Toronto, Ontario, M5J 1A7, Canada.

³Pharmaceutical Sciences Department (College of Pharmacy), Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064-3095, USA.

⁴Department of Medicine, Division of Medical Oncology, and Cedars-Sinai Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.

⁵Pharmaceutical Sciences Department (College of Pharmacy), Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064-3095, USA. Electronic address: john.buolamwini@rosalindfranklin.edu.

⁶Department of Pathology and Laboratory Medicine (College of Medicine), and the Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. Electronic address: lpfeffer@uthsc.edu.

PubMed DOI

Abstract

Glioblastoma (GBM) is a highly aggressive cancer with a dismal prognosis. Constitutively active STAT3 has a causal role in GBM progression and is associated with poor patient survival. We rationally designed a novel small molecule, SS-4, by computational modeling to specifically interact with STAT3. SS-4 strongly and selectively inhibited STAT3 tyrosine (Y)-705 phosphorylation in MT330 and LN229 G…

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