KPT-6566

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: KPT-6566
• 英文别名: 2-[[4-[[[4-(tert-Butyl)phenyl]sulfonyl]imino]-1-oxo-1,4-dihydro-2-naphthyl]thio]acetic Acid；2-[4-(4-tert-butylphenyl)sulfonylimino-1-oxonaphthalen-2-yl]sulfanylacetic acid
• 化学式: C₂₂H₂₁NO₅S₂
• 分子量: 443.544
• InChiKey: BXWWOKYIKNEEHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  135
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(tert-Butyl)-N-[3-chloro-4-oxonaphthalen-1(4H)-ylidene]benzenesulfonamide 、 巯基乙酸 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 KPT-6566
  参考文献：
  名称：

  一种PIN1抑制剂的制备工艺

  摘要：

  本发明涉及一种新型PIN1抑制剂的制备工艺，包括如下步骤：1)在有机溶剂中加入2‑氯‑1,4萘醌、4‑丁基苯硫胺和催化剂，加热，搅拌反应，TLC跟踪反应；2)将反应体系中的有机溶剂蒸干，加入石油醚，使用异丙醚打浆，抽滤后得到的固体为中间体；3)将步骤2)中得到的中间体溶于有机溶剂中，加入硫代乙醇酸和催化剂，搅拌反应；4)将步骤3)反应后的体系中有机溶剂蒸干，加入异丙醚，甲叔醚打浆，即得所述PIN1抑制剂2‑{[4‑(4‑叔丁基苯磺酰胺基)‑1‑氧代‑1,4‑二氢萘‑2‑基]硫烷基}乙酸产品。所述的制备工艺操作条件简单，后处理纯化简单，成本低，适合工业化放大。

  公开号：

  CN112479950B

文献信息

• Predictive Value of Pin1 in Cervical Low-Grade Squamous Intraepithelial Lesions and Inhibition of Pin1 Exerts Potent Anticancer Activity against Human Cervical Cancer
  作者：Guo Yan-Tong、Lu Yan、Jia Yi-Yang、Qu Hui-Nan、Qi Da、Wang Xin-Qi、Song Pei-Ye、Jin Xiang-Shu、Xu Wen-Hong、Dong Yuan、Liang Ying-Ying、Quan Cheng-Shi

  DOI：10.14336/ad.2019.0415

  日期：——

  Many oncogenes are involved in the progression from low-grade squamous intraepithelial lesions (LSILs) to high-grade squamous intraepithelial lesions (HSILs); which greatly increases the risk of cervical cancer (CC). Thus, a reliable biomarker for risk classification of LSILs is urgently needed. The prolyl isomerase Pin1 is overexpressed in many cancers and contributes significantly to tumour initiation and progression. Therefore, it is important to assess the effects of cancer therapies that target Pin1. In our study, we demonstrated that Pin1 may serve as a biomarker for LSIL disease progression and may constitute a novel therapeutic target for CC. We used a the novel Pin1 inhibitor KPT-6566, which is able to col alently bind to Pin1 and selectively target it for degradation. The results of our investigation revealed that the downregulation of Pin1 by shRNA or KPT-6566 inhibited the growth of human cervical cancer cells (CCCs). We also discovered that the use of KPT-6566 is a novel approach to enhance the therapeutic efficacy of cisplatin (DDP) against CCCs in vitro and in vivo. We showed that KPT-6566-mediated inhibition of Pin1 blocked multiple cancer-driving pathways simultaneously in CCCs. Furthermore, targeted Pin1 treatment suppressed the metastasis and invasion of human CCCs, and downregulation of Pin1 reversed the epithelial-mesenchymal transition (EMT) of CCCs via the c-Jun/slug pathway. Collectively, we showed that Pin1 may be a marker for the risk of progression to HSIL and that inhibition of Pin1 has anticancer effects against CC.