发现双重 WDR5 和 Ikaros PROTAC 降解剂作为抗癌治疗 …
WD 重复结构域 5 (WDR5) 是 MLL/KMT2A 赖氨酸甲基转移酶复合物的一个组成部分，在肿瘤发生中起着关键作用，是一个有吸引力的致癌靶点。 然而，靶向 WDR5 及其结合伴侣之间蛋白质-蛋白质相互作用 (PPI) 的抑制剂不会抑制所有 WDR5 介导的致癌功能，并且发挥相当有限的抗肿瘤作用。 在这里，我们报告了 WDR5、MS40 的小脑 (CRBN) 招募蛋白水解靶向嵌合体 (PROTAC)，它选择性地降解 WDR5 和成熟的免疫调节药物新底物 (IMiD)：CRBN、Ikaros 锌指 (IKZF)转录 …
Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti …
Here, we report a cereblon (CRBN)-recruiting proteolysis targeting chimera (PROTAC) of WDR5, MS40, which selectively degrades WDR5 and the well-established neo-substrates of immunomodulatory drugs (IMiDs):CRBN, the Ikaros zinc finger (IKZF) transcription factors IKZF1 and …
In summary, we report the discovery of a novel PROTAC that degrades both WDR5 and IKZF1/3 as a potential anti-cancer therapeutic. We also present a set of active and inactive WDR5 PROTAC analogs,...
Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti …
2022年5月7日 · In summary, we report the discovery of a novel PROTAC that degrades both WDR5 and IKZF1/3 as a potential anti-cancer therapeutic. We also present a set of active and inactive WDR5 PROTAC analogs,...
Discovery and Structure-Based Optimization of Potent and …
2019年12月20日 · Here, we describe discovery of a novel WDR5 WIN site antagonists containing a dihydroisoquinolinone bicyclic core using a structure-based design. These compounds exhibit picomolar binding affinity and selective concentration-dependent antiproliferative activities in sensitive MLL-fusion cell lines.
Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti …
In summary, we report the discovery of a novel PROTAC that degrades both WDR5 and IKZF1/3 as a potential anti-cancer therapeutic. We also present a set of active and inactive WDR5 PROTAC analogs, which represent highly useful chemical tools for studying WDR5-mediated gene regulation in biology and medicine.
Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti …
Here, we report a cereblon (CRBN)-recruiting proteolysis targeting chimera (PROTAC) of WDR5, MS40, which selectively degrades WDR5 and the well-established neo-substrates of immunomodulatory drugs (IMiDs):CRBN, the Ikaros zinc finger (IKZF) transcription factors IKZF1 and …
Jithesh Kottur - Google Scholar
J Kottur, KM White, ML Rodriguez, O Rechkoblit, R Quintana-Feliciano, ... X Yu, D Li, J Kottur, HS Kim, LE Herring, Y Yu, L Xie, X Hu, X Chen, L Cai, ... A selective WDR5 degrader inhibits acute...
Jithesh - ORCID
Jithesh Kottur via Scopus - Elsevier A strategically located serine residue is critical for the mutator activity of DNA polymerase IV from Escherichia coli Nucleic Acids Research
Design, Synthesis, and Evaluation of WD-Repeat-Containing …
Histone H3K4 methylation serves as a post-translational hallmark of actively transcribed genes and is introduced by histone methyltransferase (HMT) and its regulatory scaffolding proteins.
- 某些结果已被删除