1. Academic Validation
  2. SD-91 as A Potent and Selective STAT3 Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression

SD-91 as A Potent and Selective STAT3 Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression

  • ACS Med Chem Lett. 2021 May 10;12(6):996-1004. doi: 10.1021/acsmedchemlett.1c00155.
Haibin Zhou 1 Longchuan Bai 1 Renqi Xu 1 Donna McEachern 1 Krishnapriya Chinnaswamy 1 Ruiting Li 1 Bo Wen 1 Mi Wang 1 Chao-Yie Yang 1 Jennifer L Meagher 1 Duxin Sun 1 Jeanne A Stuckey 1 Shaomeng Wang 1
Affiliations

Affiliation

  • 1 Rogel Cancer Center, Departments of Internal Medicine and Pharmacology, Medical School, Medicinal Chemistry, College of Pharmacy, Life Sciences Institute, Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
Abstract

Signal transducer and activator of transcription 3 (STAT3) is an attractive Cancer therapeutic target. We report herein our extensive in vitro and in vivo evaluations of SD-91, the product of the hydrolysis of our previously reported STAT3 Degrader SD-36. SD-91 binds to STAT3 protein with a high affinity and displays >300-fold selectivity over Other STAT family protein members. SD-91 potently and effectively induces degradation of STAT3 protein and displays a high selectivity over Other STAT members and >7000 non-STAT proteins in cells. A single administration of SD-91 selectively depletes STAT3 protein in tumor tissues with a persistent effect. SD-91 achieves complete and long-lasting tumor regression in the MOLM-16 xenograft model in mice even with weekly administration. Hence, SD-91 is a potent, highly selective, and efficacious STAT3 Degrader for extensive evaluations for the treatment of human cancers and Other Diseases for which STAT3 plays a key role.

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