cyclo[Abu-Sar-D-N(Me)Leu-Val-D-N(Me)Leu-Ala-D-Ala-DL-N(Me)Leu-D-N(Me)Leu-D-N(Me)Val-N(Me)Bmt(E)]

• 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: cyclo[Abu-Sar-D-N(Me)Leu-Val-D-N(Me)Leu-Ala-D-Ala-DL-N(Me)Leu-D-N(Me)Leu-D-N(Me)Val-N(Me)Bmt(E)]
• 英文别名: (3R,6R,12R,15S,18R,21S,24R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone
• 化学式: C₆₂H₁₁₁N₁₁O₁₂
• 分子量: 1202.6
• InChiKey: PMATZTZNYRCHOR-AVZWOAAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  85
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  279
• 氢给体数：
  5
• 氢受体数：
  12

ADMET

毒理性

• 肝毒性

在几项大型临床试验中，环孢素治疗的开始与血清胆红素水平的轻度升高有关，通常不伴有血清ALT或碱性磷酸酶的显著增加。血清酶的升高也有描述，但较少见。最近，这些并发症似乎较为罕见，这可能是由于更谨慎地给药和监测环孢素水平。此外，在治疗没有移植众多并发症的自身免疫疾病时，环孢素治疗与高达30%的患者出现轻度血清碱性磷酸酶升高有关，但异常是无症状的，通常是自限性的，很少需要调整剂量。在几个病例系列中，环孢素治疗也与胆泥和胆石症有关。有临床明显的急性肝损伤的孤立病例报告归因于环孢素。发病时间是在开始使用环孢素后的几周内，血清酶升高的模式是胆汁淤积。一旦停止使用环孢素，恢复迅速，尚未有因环孢素引起的慢性肝炎或急性肝衰竭的报道。

In several large clinical trials, initiation of cyclosporine therapy was associated with mild elevations in serum bilirubin levels, often without significant increases in serum ALT or alkaline phosphatase. Elevations in serum enzymes were also described, but less commonly. Recently, these complications appear to be less frequent, perhaps because of more careful dosing and monitoring of cyclosporine levels. Furthermore, in treatment of autoimmune diseases without the many complications of transplantation, cyclosporine therapy has been associated with mild serum alkaline phosphatase elevations in up to 30% of patients, but the abnormalities are asymptomatic, usually self-limiting and rarely require dose adjustment. In several case series, cyclosporine therapy has also been associated with biliary sludge and cholelithiasis. Isolated case reports of clinically apparent acute liver injury have been attributed to cyclosporine. The time to onset was within a few weeks of starting cyclosporine and the pattern of serum enzyme elevations was cholestatic. Recovery was prompt once cyclosporine was stopped and cases of chronic hepatitis or acute liver failure due to cyclosporine have not been reported.

来源:LiverTox

毒理性

• 肝毒性

在大规模随机对照试验中，接受voclosporin治疗的患者的血清转氨酶水平短暂升高了3%，但在接受传统治疗的对照组中，比率相似（2%）。与环孢素类似，voclosporin治疗与碱性磷酸酶和胆红素水平的轻微增加有关，尽管这些值通常保持在正常范围内。在voclosporin上市前的研究中，没有因治疗而导致临床上明显的肝损伤的实例。然而，这种药物的临床经验有限，其他钙调神经磷酸酶抑制剂被发现会导致罕见的肝损伤，这些损伤通常是胆汁淤积性的，轻至中度严重，并且一旦停止治疗就会自行限制。

In large randomized controlled trials of voclosporin, serum aminotransferase levels were transiently elevated in 3% of patients, but rates were similar in controls receiving conventional therapy (2%). Similar to cyclosporine, voclosporin therapy is associated with minor increases in alkaline phosphatase and bilirubin levels, although values usually remain within the normal range. In the prelicensure studies of voclosporin, there were no instances of clinically apparent liver injury attributable to therapy. Clinical experience with this agent, however, has been limited and other calcineurin inhibitors have been found to cause rare instances of hepatic injury, which are generally cholestatic, mild-to-moderate in severity and self-limited in course once treatment is stopped.

来源:LiverTox

毒理性

• 致癌物分类

国际癌症研究机构致癌物：环孢素

IARC Carcinogenic Agent:Cyclosporine

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：1类：对人类致癌

IARC Carcinogenic Classes:Group 1: Carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第50卷：（1990年）药物

IARC Monographs:Volume 50: (1990) Pharmaceutical Drugs

来源:International Agency for Research on Cancer (IARC)