N-[2-[3-(4-chlorophenyl)-1-adamantyl]ethyl]-9-ethylcarbazole-3-carboxamide

• 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: N-[2-[3-(4-chlorophenyl)-1-adamantyl]ethyl]-9-ethylcarbazole-3-carboxamide
• 化学式: C₃₃H₃₅ClN₂O
• 分子量: 511.1
• InChiKey: GRUIYRYHQFRIGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  34
• 氢给体数：
  1
• 氢受体数：
  1

文献信息

• USE OF SK2 INHIBITORS IN COMBINATION WITH IMMUNE CHECKPOINT BLOCKADE THERAPY FOR THE TREATMENT OF CANCER
  申请人：Institut National de la Santé et de la Recherche Médicale (INSERM)

  公开号：EP3952850A1

  公开（公告）日：2022-02-16
• [EN] USE OF SK2 INHIBITORS IN COMBINATION WITH IMMUNE CHECKPOINT BLOCKADE THERAPY FOR THE TREATMENT OF CANCER<br/>[FR] UTILISATION D'INHIBITEURS DE SK2 EN ASSOCIATION AVEC UNE THÉRAPIE DE BLOCAGE DE POINT DE CONTRÔLE IMMUNITAIRE POUR LE TRAITEMENT DU CANCER
  申请人：INST NAT SANTE RECH MED

  公开号：WO2020208060A1

  公开（公告）日：2020-10-15

  Immune checkpoint blockade therapy is based on the inhibition of the tumor-mediated suppression of anticancer immune responses. However, the efficacy and effectiveness of said therapy vary greatly across individual patients and among different tumor types. A substantial unmet need is thus to identify novel targets that can enhance the therapeutic efficacy of the immune checkpoint blockade therapy. S1P is produced by sphingosine kinases (i.e. SK1 and SK2) that catalyze the phosphorylation of sphingosine to S1P. SK2 inhibitors were described as suitable for the treatment of cancer. However the role of SK2 in the immune tumor microenvironment has never been investigated. The inventors now showed that genetic deletion of SPHK2 leads to a delay in the melanoma tumor growth and an increase in tumor-infiltrating effector lymphocytes. In particular the increase of tumor-infiltrating effector lymphocytes in the tumor is associated with a decrease in the amount of tumor-infiltrating myeloid-derived suppressor cells. Moreover, the combination of SPHK2 deficiency with immune-checkpoint blockade leads to tumor rejection and increases survival rate. Accordingly, the present invention relates to use of SK2 inhibitors in combination with immune checkpoint blockade therapy for the treatment of cancer.