(2S,15R,16S)-15-acetyl-9-chloro-15-hydroxy-2,16-dimethylpentacyclo[9.7.0.02,8.03,5.012,16]octadeca-7,9-dien-6-one

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (2S,15R,16S)-15-acetyl-9-chloro-15-hydroxy-2,16-dimethylpentacyclo[9.7.0.02,8.03,5.012,16]octadeca-7,9-dien-6-one
• 化学式: C₂₂H₂₇ClO₃
• 分子量: 374.9
• InChiKey: DUSHUSLJJMDGTE-DGWOPZDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

毒理性

• 肝毒性

醋酸环丙孕酮治疗期间与血清酶水平升高有关，10%至14%的患者出现这种情况，但这些升高通常是短暂的、轻微的，并且常常在不调整剂量的情况下自行解决。更重要的是，醋酸环丙孕酮与许多明显的临床肝损伤和黄疸病例有关。发病时间从几个月到长达一年不等，但通常在开始治疗后的3到6个月内出现。肝损伤几乎总是肝细胞型的，血清转氨酶水平中度到明显升高，碱性磷酸酶仅有轻微增加。偶尔会发生混合性和更多胆汁淤积性损伤，预后可能更好。重要的是，与醋酸环丙孕酮使用相关的肝细胞损伤通常是严重的，出现黄疸的患者的死亡率至少为10%（这些患者通常是晚期前列腺癌的老年男性，不符合紧急肝移植的条件）。免疫过敏特征（发热、皮疹、嗜酸性粒细胞增多）不常见，自身抗体也很少。然而，一些患者似乎对皮质类固醇治疗有反应，罕见的情况下，自身免疫性肝炎样损伤归因于醋酸环丙孕酮。停用醋酸环丙孕酮后1到2周内通常可以看到改善，1到3个月内解决。尽管如此，许多例子显示，即使及时停用治疗，也会出现进行性肝损伤导致肝衰竭死亡的报道。在罕见的情况下，恢复是不完整的，患者仍有慢性肝病或肝硬化的残留证据。 可能性评分：B（可能是明显临床肝损伤的原因）。 长期使用醋酸环丙孕酮还与肝细胞癌的病例有关，通常在使用高剂量醋酸环丙孕酮或与其他激素药物（如雌激素或口服避孕药）联合治疗多年后出现。大多数肝细胞癌病例出现在非肝硬化肝脏上，并且没有其他慢性肝损伤的证据，尽管有时伴有甲胎蛋白水平的升高。在某些情况下，使用醋酸环丙孕酮多年后发现了肝癌。醋酸环丙孕酮使用与肝细胞癌之间的关联仍然有一些争议。

Cyproterone has been associated with serum enzyme elevations during therapy in 10% to 14% of patients, but these elevations are usually transient and mild and often resolve even without dose modification. More importantly, cyproterone has been associated with many instances of clinically apparent liver injury with jaundice. The time to onset has ranged from a few months to as long as a year, but typically arises within 3 to 6 months of starting treatment. The liver injury is almost always hepatocellular with moderate to marked elevations in serum aminotransferase levels and minimal increases in alkaline phosphatase. Mixed and more cholestatic injury occurs occasionally and may have a more favorable prognosis. Importantly, the hepatocellular injury associated with cyproterone use is often severe and the mortality rate of patients presenting with jaundice is at least 10% (these patients frequently being elderly men with advanced prostate cancer and not qualifying for emergency liver transplantation). Immunoallergic features (fever, rash, eosinophilia) are uncommon, as are autoantibodies. Some patients, however, appear to respond to corticosteroid therapy and rare instances of autoimmune-hepatitis like injury have been attributed to cyproterone. Improvement is usually seen within 1 to 2 weeks of stopping cyproterone and resolution within 1 to 3 months. Nevertheless, many examples of progressive liver injury leading to death from hepatic failure despite prompt discontinuation of therapy have been reported. In rare cases, recovery has been incomplete and patients have had residual evidence of chronic liver disease or cirrhosis. Likelihood score: B (likely cause of clinically apparent liver injury). Chronic therapy with cyproterone has also been linked to cases of hepatocellular carcinoma, generally arising after years of therapy with high doses of cyproterone or its combination with other hormonal agents such as estrogens or oral contraceptives. Most cases of hepatocellular carcinoma arose in a noncirrhotic liver and without other evidence of chronic liver injury, although sometimes with elevations in alpha-fetoprotein levels. In some instances, liver cancer was found years after use of cyproterone. The association of cyproterone use with hepatocellular carcinoma remains somewhat controversial.

来源:LiverTox

文献信息

• [EN] FULLY HUMAN ANTI-VEGF ANTIBODIES AND METHODS OF USING<br/>[FR] ANTICORPS ANTI-VEGF ENTIÈREMENT HUMAINS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SCHERING CORP

  公开号：WO2009055343A2

  公开（公告）日：2009-04-30

  Disclosed herein are fully human antibodies and antigen-binding fragments thereof that specifically bind human VEGF and inhibit VEGF binding to VEGF-R1 and VEGF-R2, and therefore inhibit VEGF signaling. The antibodies and antigen-binding fragments disclosed herein may be used, for example, to treat angiogenesis and conditions associated with angiogenesis both in vivo and in vitro.
• [EN] FULLY HUMAN ANTI-VEGF ANTIBODIES AND METHODS OF USING<br/>[FR] ANTICORPS ANTI-VEGF ENTIÈREMENT HUMAINS ET MÉTHODES D'UTILISATION DE CEUX-CI
  申请人：SCHERING CORP

  公开号：WO2010124009A2

  公开（公告）日：2010-10-28

  Disclosed herein are fully human antibodies and antigen-binding fragments thereof that specifically bind human VEGF and inhibit VEGF binding to VEGF-R1 and VEGF-R2, and therefore inhibit VEGF signaling. The antibodies and antigen- binding fragments disclosed herein may be used, for example, to treat angiogenesis and conditions associated with angiogenesis both in vivo and in vitro.