4-(dimethylamino)-1,10,11,12a-tetrahydroxy-7-[[methoxy(methyl)amino]methyl]-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 四环素类
• 英文名称: 4-(dimethylamino)-1,10,11,12a-tetrahydroxy-7-[[methoxy(methyl)amino]methyl]-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide
• 化学式: C₂₄H₂₉N₃O₈
• 分子量: 487.5
• InChiKey: AYUMVPHUMFKFPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  174
• 氢给体数：
  5
• 氢受体数：
  10

ADMET

毒理性

• 肝毒性

在面部痤疮的莎雷环素临床前临床试验中，血清转氨酶升高是轻微的，并不比安慰剂或比较组更频繁。没有出现临床上明显的肝损伤。尽管如此，其他四环素类抗生素，即使在低剂量使用时，也是众所周知的药物诱导肝损伤的原因，尤其是在长期给药时。米诺环素也是用于治疗痤疮的药物，是导致黄疸性肝损伤的最常见原因之一。损伤通常在治疗数月或数年后出现，并且经常表现为类似自身免疫性综合症，可以模仿红斑狼疮、类风湿性关节炎或自身免疫性肝炎。虽然莎雷环素尚未与类似的综合症相关联，但它仅短期可用，而且上市前的临床试验通常仅为12周。

In preclinical clinical trials of sarecycline in facial acne, serum aminotransferase elevations were mild and no more frequent than with placebo or comparator arms. There were no instances of clinically apparent liver injury. Nevertheless, other tetracycline antibiotics, even when used in low doses, are well known causes of drug induced liver injury particularly when given long term. Minocycline which is also used for acne is one of the most common causes of liver injury with jaundice. The injury typically arises after months or years of therapy and frequently presents as an autoimmune-like syndrome that can mimic lupus erythematosus, rheumatoid arthritis or autoimmune hepatitis. While sarecycline has not been associated with a similar syndrome, it has been available for a short time only, and the prelicensure clinical trials were generally for 12 weeks only.

来源:LiverTox