| Literature DB >> 31715132 |
Longchuan Bai1, Haibin Zhou1, Renqi Xu1, Yujun Zhao1, Krishnapriya Chinnaswamy2, Donna McEachern1, Jianyong Chen1, Chao-Yie Yang1, Zhaomin Liu1, Mi Wang1, Liu Liu1, Hui Jiang3, Bo Wen4, Praveen Kumar4, Jennifer L Meagher2, Duxin Sun4, Jeanne A Stuckey5, Shaomeng Wang6.
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.Entities:
Keywords: PROTAC; SH2 domain; STAT3; c-Myc; degrader; leukemia; lymphoma; selectivity; transcriptional factor; undruggable
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Year: 2019 PMID： 31715132 PMCID： PMC6880868 DOI： 10.1016/j.ccell.2019.10.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743