BSJ-03-123

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: BSJ-03-123
• 英文别名: N-[2-[2-[2-[2-[4-[6-[(6-acetyl-8-cyclopentyl-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-3-yl]piperazin-1-yl]ethoxy]ethoxy]ethoxy]ethyl]-2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetamide
• 化学式: C₄₇H₅₆N₁₀O₁₁
• 分子量: 937.022
• InChiKey: LUHCYAOYQIFNRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  68
• 可旋转键数：
  21
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  244
• 氢给体数：
  3
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  帕布昔利布 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 50.0h， 生成 BSJ-03-123
  参考文献：
  名称：

  Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML

  摘要：

  The design of selective small molecules is often stymied by similar ligand binding pockets. Here, we report BSJ-03-123, a phthalimide-based degrader that exploits protein-interface determinants to achieve proteome-wide selectivity for the degradation of cyclin-dependent kinase 6 (CDK6). Pharmacologic CDK6 degradation targets a selective dependency of acute myeloid leukemia cells, and transcriptomics and phosphoproteomics profiling of acute degradation of CDK6 enabled dynamic mapping of its immediate role in coordinating signaling and transcription.

  DOI：

  10.1016/j.chembiol.2018.11.006

文献信息

• COMPOUND FOR INHIBITING AND DEGRADING CDK
  申请人：SHANGHAI MEIZER PHARMACEUTICALS CO., LTD.

  公开号：US20200216450A1

  公开（公告）日：2020-07-09

  The present invention provides is a compound for inhibiting and degrading CDK. Specifically the present invention provides a compound represented by formula I, definitions of radical groups being described in the specification. The compound in the present invention has a very good inhibitory activity for the cyclin-dependent kinase (CDK), and can be used in the preparation of drugs for treating diseases related to the activity of the CDK.

  本发明提供了一种抑制和降解CDK的化合物。具体地，本发明提供了一种由公式I表示的化合物，其基团的定义在说明书中描述。本发明中的化合物具有非常好的抑制细胞周期蛋白依赖性激酶（CDK）的活性，并可用于制备用于治疗与CDK活性相关的疾病的药物。
• Substituted glutarimides as CDK inhibitors
  申请人：SHANGHAI MEIZER PHARMACEUTICALS CO., LTD.

  公开号：US11236090B2

  公开（公告）日：2022-02-01

  A compound for inhibiting and degrading cyclin-dependent kinase (CDK) is disclosed. The compound is a substituted glutarimide represented by formula I. The compound can be used in the preparation of drugs for treating diseases related to the activity of the CDK.

  本发明公开了一种用于抑制和降解细胞周期蛋白依赖性激酶（CDK）的化合物。该化合物是由式 I 代表的取代戊二酰亚胺。该化合物可用于制备治疗与 CDK 活性有关的疾病的药物。
• DEGRADATION OF CYCLIN-DEPENDENT KINASE 4/6 (CDK4/6) BY CONJUGATION OF CDK4/6 INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20210340140A1

  公开（公告）日：2021-11-04

  The present application provides bifunctional compounds, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 4 (CDK4) and/or cyclin-dependent kinase 6 (CDK6). The present application also relates to methods for the targeted degradation of CDK4 and/or CDK6 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK4 and/or
• Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML
  作者：Matthias Brand、Baishan Jiang、Sophie Bauer、Katherine A. Donovan、Yanke Liang、Eric S. Wang、Radosław P. Nowak、Jingting C. Yuan、Tinghu Zhang、Nicholas Kwiatkowski、André C. Müller、Eric S. Fischer、Nathanael S. Gray、Georg E. Winter

  DOI：10.1016/j.chembiol.2018.11.006

  日期：2019.2

  The design of selective small molecules is often stymied by similar ligand binding pockets. Here, we report BSJ-03-123, a phthalimide-based degrader that exploits protein-interface determinants to achieve proteome-wide selectivity for the degradation of cyclin-dependent kinase 6 (CDK6). Pharmacologic CDK6 degradation targets a selective dependency of acute myeloid leukemia cells, and transcriptomics and phosphoproteomics profiling of acute degradation of CDK6 enabled dynamic mapping of its immediate role in coordinating signaling and transcription.