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| Status |
Public on Nov 11, 2019 |
| Title |
A potent and selective small-molecule degrader of STAT3 achieves complete tumor regression in vivo |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. We report herein 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 represents a promising cancer therapeutic strategy.
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| Overall design |
Global gene transcription profiling was performed in MOLM-16 and SU-DHL-1 cell lines treated with DMSO, SD36 (1000 nmol/L) or SD36Me (1000 nmol/L) for 8 and 24 hours. Independent biological replicates (such as DMSO_8h and DMSO_24h) were analyzed for each cell line under each condition. DMSO-treated samples were used as controls.
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| Contributor(s) |
Yang CY, Bai L, Jiang H, Wang S |
| Citation(s) |
31715132 |
| |
| Submission date |
May 16, 2019 |
| Last update date |
Feb 10, 2020 |
| Contact name |
Chao-Yie Yang |
| E-mail(s) |
cyang26@uthsc.edu
|
| Phone |
9014486931
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| Organization name |
University of Tennessee HSC
|
| Department |
Pharmaceutical Sciences
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| Lab |
Yang
|
| Street address |
881 Madison Avenue, Rm559
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| City |
Memphis |
| State/province |
Tennessee |
| ZIP/Postal code |
38163 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA543332 |
| SRA |
SRP198674 |
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