XO44 | 2088112-70-1

• 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: XO44
• 英文别名: 4-[(4-{4-[(3-Cyclopropyl-1h-Pyrazol-5-Yl)amino]-6-[(Prop-2-Yn-1-Yl)carbamoyl]pyrimidin-2-Yl}piperazin-1-Yl)methyl]benzene-1-Sulfonyl Fluoride；4-[[4-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-6-(prop-2-ynylcarbamoyl)pyrimidin-2-yl]piperazin-1-yl]methyl]benzenesulfonyl fluoride
• CAS: 2088112-70-1
• 化学式: C₂₅H₂₇FN₈O₃S
• 分子量: 538.606
• InChiKey: ZBSPMOBILDLOCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-alpha-Cbz-L-赖氨酸 、 XO44 以 aq. phosphate buffer 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  人类激酶组中催化赖氨酸的整体反应性分析，用于共价抑制剂的开发

  摘要：

  据报道，基于芳基氟硫酸盐 (ArOSO 2 F) 的赖氨酸反应活性探针能够成功分析超过 300 种内源激酶，并提供人类激酶组可配体催化赖氨酸的全球概况。将这些亲氨基物质引入非共价 Aurora A 激酶抑制剂中产生了新型赖氨酸反应性抑制剂，该抑制剂表现出优异的体外效力和细胞活性，并具有较长的停留时间。

  DOI：

  10.1002/anie.202316394
• 作为产物：
  描述：

  methyl 2-chloro-6-((5-cyclopropyl-1H-pyrazol-3-yl)amino)pyrimidine-4-carboxylate 在 水 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.66h， 生成 XO44
  参考文献：
  名称：

  Broad-Spectrum Kinase Profiling in Live Cells with Lysine-Targeted Sulfonyl Fluoride Probes

  摘要：

  Protein kinases comprise a large family of structurally related enzymes. A major goal in kinase-inhibitor development is to selectively engage the desired kinase while; avoiding myriad off-target kinases. However, quantifying inhibitor interactions with multiple endogenous kinases in live cells remains an unmet challenge. Here, we report the design of sulfonyl fluoride probes that covalently label a broad swath of the intracellular kinome with high efficiency. Protein crystallography and mass spectrometry confirmed a chemoselective reaction between the sulfonyl fluoride and a conserved lysine in the ATP binding site. Optimized probe (XO44) covalently modified up to 133 endogenous kinases, efficiently competing with high intracellular concentrations of ATP. We employed probe 2 and label-free mass spectrometry to quantify intracellular kinase engagement by the approved drug, dasatinib. The data revealed saturable dasatinib binding to a small subset of kinase targets at clinically relevant concentrations, highlighting the utility of lysine-targeted sulfonyl fluoride probes in demanding chemoproteomic applications.

  DOI：

  10.1021/jacs.6b08536

文献信息

• CHEMICAL PROBE-DEPENDENT EVALUATION OF PROTEIN ACTIVITY AND USES THEREOF
  申请人：The University of Chicago

  公开号：US20200355673A1

  公开（公告）日：2020-11-12

  Aspects of the disclosure relate to a method for evaluating two or more target proteins of interest from the same family in a specified functional form, the method comprising: (i) contacting a composition comprising or suspected of comprising the two or more proteins of interest with a molecular construct comprising: a targeting group operatively linked to a retrieval tag; wherein the targeting group specifically binds to the specialized functional form of the two or more target proteins of interest; (ii) contacting the composition with at least two antibody-oligo constructs, wherein at least one of the constructs comprises a first antibody operatively linked to a first oligo and at least a second construct comprises a second antibody operatively linked to a second oligo; wherein the first antibody specifically binds to one of the two or more target proteins of interest and the second antibody specifically binds to the other of the two or more target proteins of interest; (iii) contacting the composition with a second molecular construct comprising a retrieval tag binder operatively linked to a retrieval oligo; (iv) incubating the composition under conditions sufficient for the ligation or annealing of the first oligo to the retrieval oligo when the first and retrieval oligos are in close proximity to each other and ligation or annealing of the second oligo to the retrieval oligo when the second and retrieval oligos are in close proximity to each other; and (v) detecting the ligated or annealed first and retrieval oligo and the ligated or annealed second and retrieval oligo.