环孢霉素A | 79217-60-0

• 物质功能分类: 生物化工 - 抑制剂 - 免疫抑制剂
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 中文名称: 环孢霉素A
• 中文别名: 环孢菌素；赛斯平；环孢素；山地明环孢灵；环孢多肽A；环孢菌素A；环孢素A；环胞霉素A
• 英文名称: SangCyA
• 英文别名: 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
• CAS: 79217-60-0
• 化学式: C₆₂H₁₁₁N₁₁O₁₂
• 分子量: 1202.6
• InChiKey: PMATZTZNYRCHOR-KMSBSJHKSA-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

代谢

肝脏，主要通过肝脏的细胞色素P450 3A酶系统广泛代谢。它也在胃肠和肾脏中以较小程度代谢。代谢物的效力明显低于母体化合物。主要代谢物（M1、M9和M4N）分别来自1-β、9-γ和4-N-去甲基位的氧化。 消除途径：消除主要是胆汁，只有6%的剂量（母药和代谢物）通过尿液排出。只有0.1%的剂量以未改变的药物形式通过尿液排出。 半衰期：双相且多变，儿童大约7小时（范围7至19小时），成人大约19小时（范围10至27小时）。

Hepatic, extensively metabolized by the cytochrome P450 3A enzyme system in the liver. It is also metabolized in the gastrointestinal tract and kidney to a lesser degree. The metabolites are significantly less potent than the parent compound. The major metabolites (M1, M9, and M4N) result from oxidation at the 1-beta, 9-gamma, and 4-N-demethylated positions, respectively. Route of Elimination: Elimination is primarily biliary with only 6% of the dose (parent drug and metabolites) excreted in the urine. Only 0.1% of the dose is excreted in the urine as unchanged drug. Half Life: Biphasic and variable, approximately 7 hours (range 7 to 19 hours) in children and approximately 19 hours (range 10 to 27 hours) in adults.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

环孢素与环孢素结合蛋白结合。该复合物随后抑制钙调神经磷酸酶，后者通常负责激活白细胞介素2的转录。环孢素还抑制淋巴因子的产生和白细胞介素的释放。在眼科应用中，确切的机制尚不清楚。环孢素乳剂被认为在因与干眼症相关的眼部炎症而假定泪液分泌受到抑制的患者中起到部分免疫调节剂的作用。

Cyclosporine binds to cyclophilin. The complex then inhibits calcineurin which is normally responsible for activating transcription of interleukin 2. Cyclosporine also inhibits lymphokine production and interleukin release. In ophthalmic applications, the precise mechanism of action is not known. Cyclosporine emulsion is thought to act as a partial immunomodulator in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca.

来源:Toxin and Toxin Target Database (T3DB)

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，通常没有血清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