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通过WDR5靶向MYC

Targeting MYC through WDR5.

作者信息

Thomas Lance R, Adams Clare M, Fesik Stephen W, Eischen Christine M, Tansey William P

机构信息

Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.

Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

出版信息

Mol Cell Oncol. 2020 Jan 10;7(2):1709388. doi: 10.1080/23723556.2019.1709388. eCollection 2020.

DOI:10.1080/23723556.2019.1709388
PMID:32158922
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7051159/
Abstract

The oncoprotein transcription factor MYC is overexpressed in most cancers and is responsible for hundreds of thousands of cancer deaths worldwide every year. MYC is also a highly validated - but currently undruggable - anti-cancer target. We recently showed that breaking the interaction of MYC with its chromatin co-factor WD repeat-containing protein 5 (WDR5) promotes tumor regression in mouse xenografts, laying the foundation for a new strategy to inhibit MYC in the clinic.

摘要

癌蛋白转录因子MYC在大多数癌症中过度表达,每年在全球导致数十万癌症死亡。MYC也是一个经过高度验证但目前无法成药的抗癌靶点。我们最近发现,破坏MYC与其染色质辅因子含WD重复序列蛋白5(WDR5)的相互作用可促进小鼠异种移植瘤中的肿瘤消退,为临床上抑制MYC的新策略奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798b/7051159/51f872166d8f/kmco-07-02-1709388-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798b/7051159/51f872166d8f/kmco-07-02-1709388-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/798b/7051159/51f872166d8f/kmco-07-02-1709388-g001.jpg

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本文引用的文献

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2
Discovery and Optimization of Salicylic Acid-Derived Sulfonamide Inhibitors of the WD Repeat-Containing Protein 5-MYC Protein-Protein Interaction.WD 重复蛋白 5-MYC 蛋白-蛋白相互作用的水杨酸衍生磺酰胺抑制剂的发现和优化。
J Med Chem. 2019 Dec 26;62(24):11232-11259. doi: 10.1021/acs.jmedchem.9b01411. Epub 2019 Dec 5.
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J Med Chem. 2023 Dec 28;66(24):16783-16806. doi: 10.1021/acs.jmedchem.3c01529. Epub 2023 Dec 12.
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