6-(5-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: 6-(5-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanoic acid
• 英文别名: 6-[5-[(3aR,4R,6aS)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoic acid
• 化学式: C₁₆H₂₇N₃O₄S
• 分子量: 357.474
• InChiKey: CMUGHZFPFWNUQT-LALPHHSUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.47
• 重原子数：
  24.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  107.53
• 氢给体数：
  4.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  利尿酸 、 6-(5-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以15%的产率得到
  参考文献：
  名称：

  Ethacrynic acid inhibits STAT3 activity through the modulation of SHP2 and PTP1B tyrosine phosphatases in DU145 prostate carcinoma cells

  摘要：

  To identify signal transducer and activator of transcription factor 3 (STAT3) inhibitors, we generated STAT3-dependent gene expression signature by analyzing gene expression profiles of DU145 cancer cells treated with STAT3 inhibitor, piperlongumine and 2-hydroxycinnamaldehyde. Then we explored gene expression signature-based strategies using a connectivity map database and identified several STAT3 inhibitors, including ethacrynic acid (EA). EA is currently used as a diuretic drug. EA inhibited STAT3 activation in DU145 prostate cancer cells and consequently decreased the levels of STAT3 target genes such as cyclin A and MCL-1. Furthermore, EA treatment inhibited tumor growth in mice xenografted with DU145 cells and decreased p-STAT3 expression in tumor tissues. Knockdown of Src homology region 2 domain-containing phosphatase-2 (SHP2) or Protein tyrosine phosphatase 1B (PTP1B) gene expression by siRNA suppressed the ability of EA to inhibit STAT3 activation. When EA was combined with an activator of SHP2 or PTP1B, p-STAT3 expression was synergistically decreased; when EA was combined with an inhibitor of SHP2 or PTP1B, p-STAT3 expression was rescued. By using an affinity pulldown assay with biotinyl-EA, EA was shown to associate with SHP2 and PTP1B in vitro. Additionally, the drug affinity responsive target stability (DARTS) assay confirmed the direct binding of EA to SHP2 and PTP1B. SHP2 is activated by EA through active phosphorylation at Y580 and direct binding to SHP2. Collectively, our results suggest that EA inhibits STAT3 activity through the modulation of phosphatases such as SHP2 and PTP1B and may be a potential anticancer drug to target STAT3 in cancer progression.

  DOI：

  10.1016/j.bcp.2020.113920
• 作为产物：
  描述：

  生物素杂质27 在 sodium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.0h， 生成 6-(5-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamido)hexanoic acid
  参考文献：
  名称：

  US2023/288411

  摘要：

  公开号：

文献信息

• A new water soluble 3,6,9-trioxaundecanedioic acid-based linker and biotinylating reagent
  作者：Ádám Bartos、Ferenc Hudecz、Katalin Uray

  DOI：10.1016/j.tetlet.2009.03.112

  日期：2009.6

  Biotinylated peptides often have low solubility in water. In this Letter, we describe a new method to synthesize a biotinylating reagent for water-solubilizing hydrophobic peptides. The biotinyl-6-aminohexanoic derivatives prepared contain a hydrophilic 3,6,9-trioxaundecanedioic acid linker moiety between the biotin and the peptide to improve the water solubility, and also to function as a spacer. The

  生物素化的肽通常在水中具有低溶解度。在这封信中，我们描述了一种合成用于水溶疏水肽的生物素化试剂的新方法。制备的生物素-6-氨基己酸衍生物在生物素和肽之间包含亲水的3,6,9-三氧杂十二烷二酸接头部分，以改善水溶性，并起间隔基的作用。合成了3,6,9-三氧杂十二烷二酸的单酯化衍生物，并将Fmoc保护的乙二胺用于连接生物素的羧基。在对包含生物素-6-氨基己酸或3,6,9-三氧杂十二烷二酸衍生物的化合物进行的比较分析中，也证明了这种新的生物素-肽结合物的亲水性。
• Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis
  作者：Yae Jin Yoon、Young-Min Han、Jiyeon Choi、Yu-Jin Lee、Jieun Yun、Su-Kyung Lee、Chang Woo Lee、Jong Soon Kang、Seung-Wook Chi、Jeong Hee Moon、Sangku Lee、Dong Cho Han、Byoung-Mog Kwon

  DOI：10.1016/j.bcp.2019.01.017

  日期：2019.5

  Metastasis is the leading cause of cancer mortality and cancer cell migration is an essential stage of metastasis. We identified benproperine (Benp, a clinically used antitussive drug) as an inhibitor of cancer cell migration and an anti-metastatic agent. Benp selectively inhibited cancer cell migration and invasion, which also suppressed metastasis of cancer cells in animal models. Actin-related protein 2/3 complex subunit 2 (ARPC2) was identified as a molecular target of Benp by affinity column chromatography with Benp-tagged Sepharose beads. Benp bound directly to ARPC2 in cells, which was validated by pull-down assay using Benp-biotin and label-free biochemical methods such as the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). Benp inhibited Arp2/3 function, showing disruption of lamellipodial structure and inhibition of actin polymerization. Unlike Arp2/3 inhibitors, Benp selectively inhibited the migration of cancer cells but not normal cells. ARPC2-knockdown cancer cells showed defective cell migration and suppressed metastasis in an animal model. Therefore, ARPC2 is a potential target for anti-metastatic therapy, and Benp has the clinical potential to block metastasis. Furthermore, Benp is a useful agent for studying the functions of the Arp2/3 complex in cancer cell migration and metastasis.