NAE Inhibitor, MLN4924

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: NAE Inhibitor, MLN4924
• 英文别名: 2-[[2-[[2-[(9-oxo-2,3-dihydro-1H-pyrrolo[2,1-b]quinazolin-7-yl)oxy]acetyl]amino]acetyl]amino]acetic acid
• 化学式: C₁₇H₁₈N₄O₆
• 分子量: 374.3
• InChiKey: BGFQHCHLBHLYBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  7

文献信息

• COMPOUNDS, COMPOSITIONS, METHODS, AND USES FOR TREATING CANCER AND IMMUNOLOGICAL DISORDERS
  申请人：IL-2RX, Inc.

  公开号：US20210252160A1

  公开（公告）日：2021-08-19

  The present disclosure provides novel polypeptide-therapeutic compound or hormone-therapeutic compound conjugates using cleavable or non-cleavable linkers, whereby the polypeptide or hormone serves to target specific cells using receptor expression on the targeted cell to bind the ligand (polypeptide or hormone) carrying the therapeutic compound unlike antibody drug conjugates. Upon binding, the ligand and the therapeutic compound (multiples of the therapeutic compound in some embodiments) enter the cell by receptor-mediated endocytosis, and release drugs conjugated to the ligand by linkers, to interact with intracellular components to enhance, restore, or block a signal transduction process. The ligands for the polypeptide-therapeutic compound or hormone-therapeutic compound conjugates include, but are not limited to: cytokines, growth factors and hormones among other proteins with corresponding cell surface specific receptors. The disorders targeted by such polypeptide-therapeutic compound or hormone-therapeutic compound conjugates include, but are not limited to: immunological disorders (e.g., allergy and autoimmune disorders) and cancer.
• COMBINATION OF LOW DOSE IL-2 AND AN INHIBITOR OF TREG IL-2R DESENSITIZATION TO TREAT AUTOIMMUNE AND ALLERGIC INFLAMMATORY DISEASES
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20210379155A1

  公开（公告）日：2021-12-09

  Provided herein are methods and compositions for treating inflammatory disease by the administration, to a patient in need thereof, of an inhibitor of IL-2R desensitization in combination with a low dose of IL-2. A low dose of interleukin-2 (IL-2) is sufficient to stimulate regulatory T lymphocytes (Tregs) without substantially inducing effector T lymphocytes (Teffs). In some embodiments, the inhibitor of IL-2R desensitization is a small molecule or drug. Is some embodiments the inhibitor is a NEDD8 activating enzyme (NAE) inhibitor. In some embodiments a combination therapy provides for a synergistic effect, where the combination of the inhibitor of IL-2R desensitization and low dose IL-2 provides an effect that is greater than the sum of either the inhibitor or low dose IL-2 administered as a single agent.