A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2019 Nov 13

PMID 31715132

Citations 216

Authors

Longchuan Bai

Haibin Zhou

Renqi Xu

Yujun Zhao

Krishnapriya Chinnaswamy

Donna McEachern

Jianyong Chen

Chao-Yie Yang

Zhaomin Liu

Mi Wang

Liu Liu

Hui Jiang

Bo Wen

Praveen Kumar

Jennifer L Meagher

Duxin Sun

Jeanne A Stuckey

Shaomeng Wang

Affiliations

Soon will be listed here.

Abstract

Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Here we report the discovery of SD-36, a small-molecule degrader of STAT3. SD-36 potently induces the degradation of STAT3 protein in vitro and in vivo and demonstrates high selectivity over other STAT members. Induced degradation of STAT3 results in a strong suppression of its transcription network in leukemia and lymphoma cells. SD-36 inhibits the growth of a subset of acute myeloid leukemia and anaplastic large-cell lymphoma cell lines by inducing cell-cycle arrest and/or apoptosis. SD-36 achieves complete and long-lasting tumor regression in multiple xenograft mouse models at well-tolerated dose schedules. Degradation of STAT3 protein, therefore, is a promising cancer therapeutic strategy.

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