methyl (2R,3R,4R,5S,6S)-3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxylate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl (2R,3R,4R,5S,6S)-3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxylate
• 英文别名: methyl (2S,3S,4R,5R,6R)-3,4,5,6-tetrahydroxyoxane-2-carboxylate
• 化学式: C₇H₁₂O₇
• 分子量: 208.168
• InChiKey: DICCNWCUKCYGNF-FDROIEKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2R,3R,4R,5S,6S)-3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxylate 、 乙酸酐 在 高氯酸 作用下， 以21%的产率得到(2S,3R,4R,5S,6S)-6-(methoxycarbonyl)tetrahydro-2Hpyran-2,3,4,5-tetrayl tetraacetate
  参考文献：
  名称：

  Oroxyloside A Overcomes Bone Marrow Microenvironment-Mediated Chronic Myelogenous Leukemia Resistance to Imatinib via Suppressing Hedgehog Pathway

  摘要：

  Imatinib (IM), as first inhibitor of the oncogenic tyrosine kinase BCR-ABL, has been widely used to treat chronic myeloid leukemia (CML) for decades in clinic. However, resistance to IM usually occurs in CML patients. The bone marrow (BM), as the predominant microenvironment of CML, secretes an abundant amount of cytokines, which may contribute to drug resistance. In current study, we utilized in vitro K562 co-culture model with BM stroma to investigate IM resistance. As a result, co-culturing of K562 with BM stroma was sufficient to cause resistance to IM, which was accompanied with the activation of hedgehog (Hh) signaling pathway and upregulation of BCR-ABL as well as its downstream proteins like phosphorylated Akt, Bcl-xL and survivin, etc. On the other hand, oroxyloside A (OAG), a metabolite of oroxylin A from the root of Scutellaria baicalensis Georgi, which had low toxic effect on K562 cells, was able to sensitize K562 cells co-cultured with BM stroma to IM treatment in vitro and in vivo. We observed that OAG suppressed Hh pathway and subsequently nuclear translocation of GLI1, followed by downregulation of BCR-ABL and its downstream effectors, thus facilitating IM to induce apoptosis of K562 cells. Together, BM microenvironment rendered K562 cells drug resistance through activating Hh signaling, however, OAG could overcome IM resistance of CML cells through inhibiting Hh-BCR-ABL axis in vitro and in vivo.

  DOI：

  10.3389/fphar.2017.00526
• 作为产物：
  描述：

  、 sodium methylate 以 甲醇 为溶剂， 反应 6.0h， 以90%的产率得到methyl (2R,3R,4R,5S,6S)-3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxylate
  参考文献：
  名称：

  Oroxyloside A Overcomes Bone Marrow Microenvironment-Mediated Chronic Myelogenous Leukemia Resistance to Imatinib via Suppressing Hedgehog Pathway

  摘要：

  Imatinib (IM), as first inhibitor of the oncogenic tyrosine kinase BCR-ABL, has been widely used to treat chronic myeloid leukemia (CML) for decades in clinic. However, resistance to IM usually occurs in CML patients. The bone marrow (BM), as the predominant microenvironment of CML, secretes an abundant amount of cytokines, which may contribute to drug resistance. In current study, we utilized in vitro K562 co-culture model with BM stroma to investigate IM resistance. As a result, co-culturing of K562 with BM stroma was sufficient to cause resistance to IM, which was accompanied with the activation of hedgehog (Hh) signaling pathway and upregulation of BCR-ABL as well as its downstream proteins like phosphorylated Akt, Bcl-xL and survivin, etc. On the other hand, oroxyloside A (OAG), a metabolite of oroxylin A from the root of Scutellaria baicalensis Georgi, which had low toxic effect on K562 cells, was able to sensitize K562 cells co-cultured with BM stroma to IM treatment in vitro and in vivo. We observed that OAG suppressed Hh pathway and subsequently nuclear translocation of GLI1, followed by downregulation of BCR-ABL and its downstream effectors, thus facilitating IM to induce apoptosis of K562 cells. Together, BM microenvironment rendered K562 cells drug resistance through activating Hh signaling, however, OAG could overcome IM resistance of CML cells through inhibiting Hh-BCR-ABL axis in vitro and in vivo.

  DOI：

  10.3389/fphar.2017.00526

文献信息

• Oroxyloside A Overcomes Bone Marrow Microenvironment-Mediated Chronic Myelogenous Leukemia Resistance to Imatinib via Suppressing Hedgehog Pathway
  作者：Xiaobo Zhang、Yicheng Liu、Lu Lu、Shaoliang Huang、Youxiang Ding、Yi Zhang、Qinglong Guo、Zhiyu Li、Li Zhao

  DOI：10.3389/fphar.2017.00526

  日期：——

  Imatinib (IM), as first inhibitor of the oncogenic tyrosine kinase BCR-ABL, has been widely used to treat chronic myeloid leukemia (CML) for decades in clinic. However, resistance to IM usually occurs in CML patients. The bone marrow (BM), as the predominant microenvironment of CML, secretes an abundant amount of cytokines, which may contribute to drug resistance. In current study, we utilized in vitro K562 co-culture model with BM stroma to investigate IM resistance. As a result, co-culturing of K562 with BM stroma was sufficient to cause resistance to IM, which was accompanied with the activation of hedgehog (Hh) signaling pathway and upregulation of BCR-ABL as well as its downstream proteins like phosphorylated Akt, Bcl-xL and survivin, etc. On the other hand, oroxyloside A (OAG), a metabolite of oroxylin A from the root of Scutellaria baicalensis Georgi, which had low toxic effect on K562 cells, was able to sensitize K562 cells co-cultured with BM stroma to IM treatment in vitro and in vivo. We observed that OAG suppressed Hh pathway and subsequently nuclear translocation of GLI1, followed by downregulation of BCR-ABL and its downstream effectors, thus facilitating IM to induce apoptosis of K562 cells. Together, BM microenvironment rendered K562 cells drug resistance through activating Hh signaling, however, OAG could overcome IM resistance of CML cells through inhibiting Hh-BCR-ABL axis in vitro and in vivo.