6NUQ

Stat3 Core in complex with compound SI109

Summary for 6NUQ

• Entry DOI: 10.2210/pdb6nuq/pdb
• Descriptor: Signal transducer and activator of transcription 3, [(2-{[(5S,8S,10aR)-3-acetyl-8-({(2S)-5-amino-1-[(diphenylmethyl)amino]-1,5-dioxopentan-2-yl}carbamoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl]carbamoyl}-1H-indol-5-yl)(difluoro)methyl]phosphonic acid (non-preferred name) (3 entities in total)
• Functional Keywords: stat3, activator, transcription, transcription-transcription inhibitor complex, transcription/transcription inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 65253.75

Authors

Meagher, J.L.,Stuckey, J.A. (deposition date: 2019-02-01, release date: 2019-12-04, Last modification date: 2023-10-11)

Primary citation

Bai, L.,Zhou, H.,Xu, R.,Zhao, Y.,Chinnaswamy, K.,McEachern, D.,Chen, J.,Yang, C.Y.,Liu, Z.,Wang, M.,Liu, L.,Jiang, H.,Wen, B.,Kumar, P.,Meagher, J.L.,Sun, D.,Stuckey, J.A.,Wang, S.
A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo.
Cancer Cell, 36:498-511.e17, 2019

PubMed 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.

PubMed: 31715132
DOI: 10.1016/j.ccell.2019.10.002

Experimental method

X-RAY DIFFRACTION (3.15 Å)