α-Gal BOEL | 1821461-84-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: α-Gal BOEL
• 英文别名: (9Z,9'Z)-(2R)-3-(((2-(6-((3-(((2R,3R,4R,5S,6R)-3-acetamido-5-(((2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)propyl)amino)-6-oxohexanamido)ethoxy)(hydroxy)phosphoryl)oxy)propane-1,2-diyl bis(octadec-9-enoate)；Agi-134；[(2R)-3-[2-[[6-[3-[(2R,3R,4R,5S,6R)-3-acetamido-5-[(2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-4-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxypropylamino]-6-oxohexanoyl]amino]ethoxy-hydroxyphosphoryl]oxy-2-[(Z)-octadec-9-enoyl]oxypropyl] (Z)-octadec-9-enoate
• CAS: 1821461-84-0
• 化学式: C₇₀H₁₂₆N₃O₂₆P
• 分子量: 1456.75
• InChiKey: ZJYQGJWRGLACDM-UNBAAJOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  100
• 可旋转键数：
  60
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  433
• 氢给体数：
  13
• 氢受体数：
  26

反应信息

• 作为产物：
  描述：

  DOPE-Ad-ONSu 、 3-aminopropyl 4-O-[3-O-(α-D-galactopyranosyl)-β-D-galactopyranosyl]-2-acetamido-2-deoxy-β-D-glucopyranoside 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以84%的产率得到α-Gal BOEL
  参考文献：
  名称：

  [EN] GLYCOLIPID CONTAINING COMPOSITIONS FOR USE IN THE TREATMENT OF TUMOURS
  [FR] COMPOSITIONS CONTENANT DES GLYCOLIPIDES POUR LEUR UTILISATION DANS LE TRAITEMENT DE TUMEURS

  摘要：

  本发明涉及含有α-Gal BOEL的制药组合物，用于治疗患有肿瘤的患者。本发明还涉及使用该组合物治疗肿瘤的方法。本发明揭示了在α-Gal BOEL肿瘤内注射后，天然抗-Gal抗体与新表达的肿瘤α-Gal表位结合，引起炎症反应，导致抗-Gal抗体介导的肿瘤细胞被吞噬并被抗原呈递细胞摄取。这些抗原呈递细胞迁移到淋巴结并激活肿瘤特异性T细胞，从而将治疗的肿瘤病灶转化为原位自体肿瘤疫苗。该疗法可应用于具有多个病灶的患者以及在肿瘤切除前的新辅助疗法中。除了治疗的肿瘤的回归和/或破坏外，这样的疫苗还有助于免疫介导破坏在治疗的肿瘤切除期间无法检测到的微小转移灶。本发明还教导了通过使用抑制免疫检查点分子活性的抗体来增强抗肿瘤α-Gal BOEL治疗的方法。

  公开号：

  WO2015170121A1

文献信息

• [EN] AGI-134 COMBINED WITH A CHECKPOINT INHIBITOR FOR THE TREATMENT OF SOLID TUMORS<br/>[FR] AGI-134 COMBINÉE À UN INHIBITEUR DE POINT DE CONTRÔLE POUR LE TRAITEMENT DE TUMEURS SOLIDES
  申请人：BIOLINERX LTD

  公开号：WO2019229745A1

  公开（公告）日：2019-12-05

  A method of treating a tumor in a subject is disclosed. The method comprises administering to the subject a therapeutically effective amount of: i) Pembrolizumab; and ii) a lipid having a structural formula as illustrated in Figure 1 (AGI-134).

  本发明揭示了一种治疗受体者肿瘤的方法。该方法包括向受体者投予治疗有效量的：i）Pembrolizumab；和ii）具有如图1所示的结构式的脂质（AGI-134）。
• [EN] GLYCOLIPID CONTAINING COMPOSITIONS FOR USE IN THE TREATMENT OF TUMOURS<br/>[FR] COMPOSITIONS CONTENANT DES GLYCOLIPIDES POUR LEUR UTILISATION DANS LE TRAITEMENT DE TUMEURS
  申请人：AGALIMMUNE LTD

  公开号：WO2015170121A1

  公开（公告）日：2015-11-12

  The invention relates to pharmaceutical compositions comprising α-Gal BOEL for use in treating patients with tumours. The invention also relates to methods of treating tumours using said compositions. The invention discloses that following intratumoural injection of α- Gal BOEL, binding of the natural anti-Gal antibody to de novo expressed tumoural α-Gal epitopes induces inflammation resulting in an anti-Gal antibody mediated opsonization of tumour cells and their uptake by antigen presenting cells. These antigen presenting cells migrate to draining lymph nodes and activate tumour specific T cells thereby converting the treated tumour lesions into in situ autologous tumour vaccines. This therapy can be applied to patients with multiple lesions and in neo-adjuvant therapy to patients before tumour resection. In addition to the regression and/or destruction of the treated tumour, such a vaccine will help in the immune mediated destruction of micrometastases that are not detectable during the removal of the treated tumour. The invention further teaches the enhancement of anti-tumour α-Gal BOEL treatment by the use of antibodies that inhibit the activity of immunological checkpoints molecules.

  本发明涉及含有α-Gal BOEL的制药组合物，用于治疗患有肿瘤的患者。本发明还涉及使用该组合物治疗肿瘤的方法。本发明揭示了在α-Gal BOEL肿瘤内注射后，天然抗-Gal抗体与新表达的肿瘤α-Gal表位结合，引起炎症反应，导致抗-Gal抗体介导的肿瘤细胞被吞噬并被抗原呈递细胞摄取。这些抗原呈递细胞迁移到淋巴结并激活肿瘤特异性T细胞，从而将治疗的肿瘤病灶转化为原位自体肿瘤疫苗。该疗法可应用于具有多个病灶的患者以及在肿瘤切除前的新辅助疗法中。除了治疗的肿瘤的回归和/或破坏外，这样的疫苗还有助于免疫介导破坏在治疗的肿瘤切除期间无法检测到的微小转移灶。本发明还教导了通过使用抑制免疫检查点分子活性的抗体来增强抗肿瘤α-Gal BOEL治疗的方法。
• Glycolipid containing compositions for use in the treatment of tumors
  申请人：Agalimmune Limited (GB/GB)

  公开号：US10092586B2

  公开（公告）日：2018-10-09

  The invention relates to pharmaceutical compositions comprising α-Gal BOEL for use in treating patients with tumors. The invention also relates to methods of treating tumors using said compositions. The invention discloses that following intratumoral injection of α-Gal BOEL, binding of the natural anti-Gal antibody to de novo expressed tumoral α-Gal epitopes induces inflammation resulting in an anti-Gal antibody mediated opsonization of tumor cells and their uptake by antigen presenting cells. These antigen presenting cells migrate to draining lymph nodes and activate tumor specific T cells thereby converting the treated tumor lesions into in situ autologous tumor vaccines. This therapy can be applied to patients with multiple lesions and in neo-adjuvant therapy to patients before tumor resection. In addition to the regression and/or destruction of the treated tumor, such a vaccine will help in the immune mediated destruction of micrometastases that are not detectable during the removal of the treated tumor. The invention further teaches the enhancement of anti-tumor α-Gal BOEL treatment by the use of antibodies that inhibit the activity of immunological checkpoints molecules.

  本发明涉及用于治疗肿瘤患者的包含 α-Gal BOEL 的药物组合物。本发明还涉及使用所述组合物治疗肿瘤的方法。本发明披露，瘤内注射α-Gal BOEL 后，天然抗-Gal 抗体与新表达的肿瘤α-Gal 表位结合，诱发炎症，导致抗-Gal 抗体介导的肿瘤细胞疏松，并被抗原呈递细胞吸收。这些抗原呈递细胞迁移到引流淋巴结，激活肿瘤特异性 T 细胞，从而将治疗过的肿瘤病灶转化为原位自体肿瘤疫苗。这种疗法可用于多病灶患者，也可用于肿瘤切除术前的新辅助治疗。除了治疗肿瘤的消退和/或破坏外，这种疫苗还有助于免疫介导的微转移灶的破坏，这些微转移灶在切除治疗肿瘤时无法检测到。本发明进一步教导通过使用抑制免疫检查点分子活性的抗体来增强抗肿瘤α-Gal BOEL 治疗。
• GLYCOLIPID CONTAINING COMPOSITIONS FOR USE IN THE TREATMENT OF TUMOURS
  申请人：Agalimmune Limited

  公开号：EP3139931A1

  公开（公告）日：2017-03-15