0J0U795Mfz | 2412193-87-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 0J0U795Mfz
• 英文别名: (7R,8R)-8-[(2S,5S,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,10,16,20,23,25,28,31-nonamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-8-hydroxy-7-methyloctanoic acid
• CAS: 2412193-87-2
• 化学式: C₆₄H₁₁₅N₁₁O₁₄
• 分子量: 1262.68
• InChiKey: IHYTVKXOCVXPQF-XZYMMQACSA-N

物化性质

• 沸点：
  1340.5±65.0 °C(Predicted)
• 密度：
  1.036±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  89
• 可旋转键数：
  19
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  316
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  H2N-PEG2000-OMe 、 0J0U795Mfz 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙腈 为溶剂， 以0.4 g的产率得到
  参考文献：
  名称：

  [EN] CYCLOSPORINE COMPOSITIONS AND METHODS OF USE
  [FR] COMPOSITIONS DE CYCLOSPORINE ET MÉTHODES D'UTILISATION

  摘要：

  本文公开了环孢霉素化合物及其在治疗、预防或改善葡萄糖不耐症方面的使用方法，其中该化合物抑制N-甲酰肽受体1（FPR1）的活性。

  公开号：

  WO2022225839A1
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 以82.03 mg的产率得到0J0U795Mfz
  参考文献：
  名称：

  Cyclosporin A-Based PROTACs Can Deplete Abundant Cellular Cyclophilin A without Suppressing T Cell Activation

  摘要：

  Cyclophilin A (CypA), the cellular receptor of the immunosuppressant cyclosporin A (CsA), is an abundant cytosolic protein and is involved in a variety of diseases. For example, CypA supports cancer proliferation and mediates viral infections, such as the human immunodeficiency virus 1 (HIV-1). Here, we present the design of PROTAC (proteolysis targeting chimera) compounds against CypA to induce its intracellular proteolysis and to investigate their effect on immune cells. Interestingly, upon connecting to E3 ligase ligands, both peptide-based low-affinity binders and CsA-based high-affinity binders can degrade CypA at nM concentration in HeLa cells and fibroblast cells. As the immunosuppressive effect of CsA is not directly associated with the binding of CsA to CypA but the inhibition of phosphatase calcineurin by the CypA:CsA complex, we investigated whether a CsA-based PROTAC compound could induce CypA degradation without affecting the activation of immune cells. P3, the most efficient PROTAC compound discovered from this study, could deplete CypA in lymphocytes without affecting cell proliferation and cytokine production. This work demonstrates the feasibility of the PROTAC approach in depleting the abundant cellular protein CypA at low drug dosage without affecting immune cells, allowing us to investigate the potential therapeutic effects associated with the endogenous protein in the future.

  DOI：

  10.3390/molecules29122779

文献信息

• WO2020041378A5
  申请人：——

  公开号：WO2020041378A5

  公开（公告）日：2022-08-23