39-O-desmethoxy-rapamycin | 821792-15-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: 39-O-desmethoxy-rapamycin
• 英文别名: 39-desmethoxyrapamycin；BC-210；41-desmethoxy-rapamycin
• CAS: 821792-15-8
• 化学式: C₅₀H₇₇NO₁₂
• 分子量: 884.161
• InChiKey: DIEORUOOFDNDCG-AUFCVUAVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.56
• 重原子数：
  63.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  186.2
• 氢给体数：
  3.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  39-O-desmethoxy-rapamycin 、 2-(叔丁基二甲基硅烷基)氧基乙醇三氟甲磺酸酯 在 2,6-二叔丁基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成
  参考文献：
  名称：

  WO2006/95185

  摘要：

  公开号：
• 作为产物：
  描述：

  环己甲酸 在 S_. hygroscopicus MG₂-10 [IJMNOQLhis] 作用下， 反应 48.0h， 生成 39-O-desmethoxy-rapamycin
  参考文献：
  名称：

  WO2006/95185

  摘要：

  公开号：

文献信息

• BIOMARKERS FOR SENSITIVITY TO ANTI-IGF1R THERAPY
  申请人：Wang Yan

  公开号：US20110091524A1

  公开（公告）日：2011-04-21

  The present invention provides, for example, methods for conveniently determining if a cancerous condition in a subject will be responsive to an IGF1R inhibitor. The invention includes patient selection methods and methods of treatment.

  本发明提供了方便确定受试者的癌症状况是否对IGF1R抑制剂具有响应的方法。该发明包括患者选择方法和治疗方法。
• FDG-PET EVALUATION OF EWING'S SARCOMA SENSITIVITY
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20130243692A1

  公开（公告）日：2013-09-19

  This invention relates to methods for evaluating the efficacy of an IGF1R inhibitor, such as an anti-IGF1R antibody, for the treatment of an Ewing's sarcoma tumor by determining the level of tumoral glucose metabolism. Tumoral glucose metabolism is determining at an early point in the treatment regimen by any of several methods known in the art including FDG-PET/CT scan.

  本发明涉及一种评估IGF1R抑制剂（如抗IGF1R抗体）对Ewing肉瘤肿瘤治疗疗效的方法，通过确定肿瘤葡萄糖代谢水平来进行。肿瘤葡萄糖代谢可以通过艺术中已知的几种方法之一（包括FDG-PET/CT扫描）在治疗方案的早期阶段进行确定。
• HISTONE H2AX (HH2AX) BIOMARKER FOR FTI SENSITIVITY
  申请人：Basso-Porcaro Andrea Dawn

  公开号：US20110009387A1

  公开（公告）日：2011-01-13

  The present invention relates e.g., to methods for predicting cellular sensitivity to farnesyl protein transferase inhibitors, such as lonafarnib; manumycin A; FTI-276; L-744832; BMS-214662; tipifarnib; BMS-316810K. The methods involve determining if malignant cells exhibit increased expression. of phosphorylated histone H2Ax following contact of one or more of said cells with said inhibitor.

  本发明涉及例如，用于预测细胞对法尼酰蛋白转移酶抑制剂（如洛纳法尼布、马努霉素A、FTI-276、L-744832、BMS-214662、替匹法尼布、BMS-316810K）的敏感性的方法。该方法涉及确定恶性细胞是否在与该抑制剂中的一个或多个细胞接触后表现出磷酸化组蛋白H2Ax的表达增加。
• Hybrid Inhibitors of Phosphatidylinositol 3-Kinase (PI3K) and the Mammalian Target of Rapamycin (mTOR): Design, Synthesis, and Superior Antitumor Activity of Novel Wortmannin−Rapamycin Conjugates
  作者：Semiramis Ayral-Kaloustian、Jianxin Gu、Judy Lucas、Michael Cinque、Christine Gaydos、Arie Zask、Inder Chaudhary、Jianyao Wang、Li Di、Mairead Young、Mark Ruppen、Tarek S. Mansour、James J. Gibbons、Ker Yu

  DOI：10.1021/jm901427g

  日期：2010.1.14

  Hyperactivation of the P13K/AKT/mTOR signaling pathway is common in cancer, and P13K and mTOR act synergistically in promoting tumor growth, survival, and resistance to chemotherapy. Thus, combined targeting of P13K and mTOR presents an opportunity for robust and synergistic anticancer efficacy. 17-Hydroxywortinannin (2a) analogues conjugated to rapamycin (3a) analogues viaa prodrug linker are uniquely positioned for this approach. Out- efforts led to the discovery of diester-linked conjugates that, upon in vivo hydrolysis, released two highly potent inhibitors. Conjugate 7c provided enhanced solubility relative to 3a and to an equivalent mixture of 3a and 9a and demonstrated profound activity in U87MG mouse xenografts, achieving an MED of 1.5 mg/kg, following weekly intravenous dosing. At 15 mg/kg, 7c completely inhibited the growth of HT29 tumors, whereas an equivalent mixture of the inhibitors was poorly tolerated. In the A498 renal tumor model, 7c exhibited superior efficacyover3aor9a whenadministered asa singleagentorincombination with bevacizumab. Thus, We have uncovered it novel approach to target both P13K and mTOR via hybrid inhibitors, leading to it broader and more robust anticanccr efficacy.
• Regioselective lipase-catalyzed acylation of 41-desmethoxy-rapamycin without vinyl esters
  作者：Thomas Storz、Jianxin Gu、Bogdan Wilk、Eric Olsen

  DOI：10.1016/j.tetlet.2010.08.020

  日期：2010.10

  Selective lipase-catalyzed acylation of 41-desmethoxyrapamycin has been achieved with a quaternary carboxylic acid avoiding the use of vinyl ester activation. Among the acyl donors investigated, the novel butanedione-monooxime and the N-acetylhydroxamate ester proved to be the most efficient donors, comparable in reactivity to the undesired vinyl ester and allowing selective, preparative acylation on gram scale in excellent yields. These new donors are proposed as sustainable and process-friendly alternatives to the widely used vinyl ester substrate activation in lipase-catalyzed acylations of secondary alcohols. (C) 2010 Elsevier Ltd. All rights reserved.