6-nitrotryptophan | 36802-39-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6-nitrotryptophan
• 英文别名: NSC 65763；6-Nitro-L-tryptophan, 17；2-azaniumyl-3-(6-nitro-1H-indol-3-yl)propanoate
• CAS: 36802-39-8
• 化学式: C₁₁H₁₁N₃O₄
• 分子量: 249.226
• InChiKey: AWLWPSSHYJQPCH-UHFFFAOYSA-N

物化性质

• 沸点：
  534.7±50.0 °C(Predicted)
• 密度：
  1.541±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  DL-色氨酸 在 硝酸 、 溶剂黄146 、 尿素 作用下， 反应 13.5h， 生成 4-nitrotryptophan 、 6-nitrotryptophan
  参考文献：
  名称：

  Boron Accumulation in Brain Tumor Cells through Boc-Protected Tryptophan as a Carrier for Boron Neutron Capture Therapy

  摘要：

  Boron neutron capture therapy (BNCT) is a binary therapeutic approach. Nonradioactive boron-10 atoms accumulated in tumor cells combining with the neutron beams produce two highly energetic particles that could eradicate the cell that takes it and the neighboring cells. Small molecules that carry boron atom, e.g. 5- and 6-boronated and 2,7-diboronated tryptophans, were assessed for their boron accumulation in U87-MG, LN229, and 3T3 for BNCT. TriBoc tryptophan, TB-6-BT, shows boron-10 at 300 ppm in both types of tumor cells with a tumor to normal ratio (T/N) of 5.19-5.25 (4 h). TB-5-BT and DBA-5-BT show boron-10 at 300 ppm (2 h) in U87-MG cells. TB-5-BT exerts a T/N of >9.66 (1 h) in LN229 compared with the current clinical boronophenyl alanine with a highest T/N of 2.3 (1 h) and accumulation concentration of <50 ppm. TB-5-BT and TB-6-BT warrant further animal study.

  DOI：

  10.1021/acsmedchemlett.0c00064

文献信息

• CD28H STIMULATION ENHANCES NK CELL KILLING ACTIVITIES
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：EP3800201A1

  公开（公告）日：2021-04-07

  CD28H (TMIGD2 or IGPR-1) belongs to the CD28 family and is a transmembrane protein with an immunoglobulin-like extracellular domain, a transmembrane domain and a cytoplasmic tail. The main objective of the inventors was to evaluate the consequences of CD28H stimulation on NK with a monoclonal anti-CD28H antibody (clone 4-5) known to activate T cells. The inventors show that circulating CD56bright and CD56dim NK cells express the same level of CD28H. Circulating CD28H+ NK cells are more activated than CD28Hneg, in fact NK CD28H+ cells express more CD69, NKp30 and Nkp46. The agonist anti-CD28H mAb induces a calcium flux in NK cells while the blocking mAb does not. Calcium flux evaluation shows that CD28H synergize with NKP46 but not with CD16. After an overnight stimulation with the agonist anti-CD28H mAb, NK cells express more CD69, Nkp30, NKG2D and less CD16 compared to a control condition with an isotype mAb. This reflects a very strong activation of NK cells. Moreover, the CD28H-primed NK cells treated with the agonistic anti-CD28H mAb secret more granzyme B and more IFN-g in presence of K562. CD28H-primed NK cells increase their cytotoxic capacities against tumor cell lines. When used in vivo in a xeno-GVHD model in NSG-SGM3 mice, the agonistic anti-CD28H mAb increases the frequency of NK cells suggesting a potential role of CD28H in NK homeostasis. Thus CD28H is a strong activator of NK cells and is the potential new therapeutic target for cancer immunotherapy

  CD28H（TMIGD2 或 IGPR-1）属于 CD28 家族，是一种跨膜蛋白，具有免疫球蛋白样胞外结构域、跨膜结构域和胞质尾部。发明者的主要目的是评估 CD28H 刺激 NK 与已知能激活 T 细胞的单克隆抗 CD28H 抗体（克隆 4-5）的后果。发明人发现，循环中 CD56bright 和 CD56dim NK 细胞表达相同水平的 CD28H。循环中的 CD28H+ NK 细胞比 CD28Hneg 更活化，事实上，NK CD28H+ 细胞表达更多的 CD69、NKp30 和 Nkp46。激动剂抗 CD28H mAb 能诱导 NK 细胞中的钙通量，而阻断 mAb 则不能。钙通量评估显示，CD28H 与 NKP46 有协同作用，但与 CD16 没有协同作用。与使用同种型 mAb 的对照组相比，在使用激动剂抗 CD28H mAb 刺激过夜后，NK 细胞表达更多的 CD69、Nkp30 和 NKG2D，而表达更少的 CD16。这反映出 NK 细胞被强烈激活。此外，在有 K562 存在的情况下，用激动抗 CD28H mAb 处理的 CD28H 催化 NK 细胞会分泌更多的颗粒酶 B 和更多的 IFN-g。CD28H刺激的NK细胞提高了对肿瘤细胞株的细胞毒能力。在NSG-SGM3小鼠体内的异种-GVHD模型中，激动抗CD28H mAb可增加NK细胞的频率，这表明CD28H在NK平衡中的潜在作用。因此，CD28H 是 NK 细胞的强激活剂，是癌症免疫疗法的潜在新治疗靶点。
• Methods for enhancing the potency of the immune checkpoint inhibitors
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US10822415B2

  公开（公告）日：2020-11-03

  The present invention relates to methods for enhancing the potency of the immune checkpoint inhibitors. In particular, the present invention relates to a method for enhancing the potency of an immune checkpoint inhibitor administered to a subject as part of a treatment regimen, the method comprising administering a pharmaceutically effective amount of a SK1 inhibitor to a subject in combination with the immune checkpoint inhibitor.

  本发明涉及增强免疫检查点抑制剂效力的方法。特别是，本发明涉及一种增强作为治疗方案一部分施用给受试者的免疫检查点抑制剂效力的方法，该方法包括将药学有效量的SK1抑制剂与免疫检查点抑制剂联合施用给受试者。
• Methods and pharmaceutical composition for the treatment of cancer
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US10918737B2

  公开（公告）日：2021-02-16

  The present invention relates to methods and pharmaceutical composition for the treatment of cancer. In particular, the present invention relates to a method for enhancing the potency of an immune checkpoint inhibitor administered to a subject as part of a treatment regimen for cancer, the method comprising: administering a pharmaceutically effective amount of a TNFα blocking agent to a subject in combination with the immune checkpoint inhibitor.

  本发明涉及治疗癌症的方法和药物组合物。特别是，本发明涉及一种用于增强作为癌症治疗方案一部分给受试者施用的免疫检查点抑制剂效力的方法，该方法包括：给受试者施用药学上有效量的 TNFα 阻断剂与免疫检查点抑制剂。
• Methods for determining the metabolic status of lymphomas
  申请人：INSERM (Institut National de la Sante et de la Recherche Medicale)

  公开号：US10947598B2

  公开（公告）日：2021-03-16

  Provided is an in vitro method for determining the metabolic status of a lymphoma comprising a step of determining the level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression in lymphoma cells, wherein a low level of GAPDH expression is indicative of oxidative phosphorylation (OXPHOS) status. Also provided is an in vitro method for predicting the responsiveness of a patient afflicted with a lymphoma to a treatment with a metabolic inhibitor selected from the group consisting of mitochondrial metabolic inhibitors and glutamine metabolism inhibitors comprising a step of determining the level of GAPDH expression in lymphoma cells obtained from said patient, wherein a low level of GAPDH expression is predictive of a response to a treatment with a metabolic inhibitor.

  本发明提供了一种用于确定淋巴瘤代谢状态的体外方法，包括确定淋巴瘤细胞中甘油醛-3-磷酸脱氢酶（GAPDH）表达水平的步骤，其中低水平的 GAPDH 表达表明氧化磷酸化（OXPHOS）状态。还提供了一种体外方法，用于预测淋巴瘤患者对选自线粒体代谢抑制剂和谷氨酰胺代谢抑制剂组成的组的代谢抑制剂治疗的反应性，包括确定从所述患者处获得的淋巴瘤细胞中 GAPDH 表达水平的步骤，其中低水平的 GAPDH 表达可预测对代谢抑制剂治疗的反应。
• Methods and pharmaceutical compositions for enhancing CD8+ T cell-dependent immune responses in subjects suffering from cancer
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE)

  公开号：US11078277B2

  公开（公告）日：2021-08-03

  The present invention relates to methods and pharmaceutical compositions for enhancing CD8+ T cell-dependent immune responses in subjects suffering from cancer. In particular, the present invention relates to a method of enhancing the CD8+ T cell-dependent immune response in a subject suffering from cancer comprising administering to the subject a therapeutically effective amount of an agent capable of increasing intra-tumoral ceramide content.

  本发明涉及增强癌症患者 CD8+ T 细胞依赖性免疫反应的方法和药物组合物。特别是，本发明涉及一种增强癌症患者 CD8+ T 细胞依赖性免疫应答的方法，该方法包括向该患者施用治疗有效量的能够增加肿瘤内神经酰胺含量的制剂。