(2S)-2-[4-[4-(4,5-dihydroxy-4,6-dimethyloxan-2-yl)oxy-5-hydroxy-6-methyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-3-[(1S,3S,4R)-3,4-dihydroxy-1-methoxy-2-oxopentyl]-6-[4-(4,5-dihydroxy-6-methyloxan-2-yl)oxy-5-hydroxy-6-methyloxan-2-yl]oxy-8,9-dihydroxy-7-methyl-3,4-dihydro-2H-anthracen-1-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S)-2-[4-[4-(4,5-dihydroxy-4,6-dimethyloxan-2-yl)oxy-5-hydroxy-6-methyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-3-[(1S,3S,4R)-3,4-dihydroxy-1-methoxy-2-oxopentyl]-6-[4-(4,5-dihydroxy-6-methyloxan-2-yl)oxy-5-hydroxy-6-methyloxan-2-yl]oxy-8,9-dihydroxy-7-methyl-3,4-dihydro-2H-anthracen-1-one
• 化学式: C₅₂H₇₆O₂₄
• 分子量: 1085.1
• InChiKey: CFCUWKMKBJTWLW-ARMLCFENSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  76
• 可旋转键数：
  15
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  358
• 氢给体数：
  11
• 氢受体数：
  24

ADMET

毒理性

• 肝毒性

使用plicamycin进行化疗会导致几乎所有治疗超过1到2天并在治疗期间接受监测的患者血清酶水平升高。血清ALT、AST和LDH值在第一次输注后的3天内开始上升，并在7到10天内达到峰值，水平为正常上限(ULN)的5到500倍。然而，这些升高是暂时的，在1到3周内解决，很少伴有症状或黄疸。在这些发作期间进行的肝脏活检通常显示中央小叶坏死和充血。随着治疗的重复进行，升高的情况通常会继续发生，程度相同或更轻。有一例报告称，一名患者因非恶性高钙血症接受全剂量plicamycin治疗4天后，出现了急性肝衰竭，这提示可能是缺血性肝炎或窦状阻塞综合征。除此之外，尽管血清酶升高程度为中等至严重，但它们是暂时的且良性。

Chemotherapy with plicamycin causes serum enzyme elevations in almost all patients who are treated for more than 1 or 2 days and who are monitored during therapy. Serum ALT, AST and LDH values begin to rise within 3 days of the first infusion and peak within 7 to 10 days at levels of 5 to 500 times the upper limit of the normal range (ULN). The elevations, however, are transient and resolve within 1 to 3 weeks and are rarely associated with symptoms or jaundice. Liver biopsies taken during these episodes usually demonstrate centrolobular necrosis and congestion. With repeated courses, elevations continue to occur generally to the same or lesser degree. A single instance of acute liver failure arising within days of therapy that was suggestive of ischemic hepatitis or sinusoidal obstruction syndrome has been reported in a patient treated with full doses of plicamycin for 4 days for nonmalignant hypercalcemia. Otherwise, the serum enzyme elevations, despite being moderate to severe, are transient and benign.

来源:LiverTox

毒理性

• 相互作用

普卡霉素引起的低凝血酶原血症可能会增加香豆素类和茚满二酮衍生物抗凝剂的活动性，并可能增加接受肝素或溶栓药物治疗的患者的出血风险；不推荐同时使用。

Plicamycin-induced hypoprothrombinemia may increase the activity of coumarin- and indandione-derivative anticoagulants and may increase the risk of bleeding in patient receiving heparin or thrombolytic agents; concurrent use is not recommended.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用非甾体抗炎药、阿司匹林、右旋糖酐、双嘧达莫、磺吡拉宗或丙戊酸与普卡霉素可能会增加出血风险，因为这些药物单独或与普卡霉素联合使用时，可能会通过增加或协同作用降低血液凝固能力，即抑制血小板聚集，同时普卡霉素和大剂量阿司匹林可能会诱导低凝血酶原血症；此外，阿司匹林、非甾体抗炎药或磺吡拉宗的胃肠道溃疡性或出血倾向可能会增加接受普卡霉素治疗患者的出血风险。

Concurrent use /of nonsteroidal anti-inflammatory drugs, aspirin, dextran, dipyridamole, sulfinpyrazone, or valproic acid/ with plicamycin may increase the risk of hemorrhage because of additive or multiple actions, which may decrease the blood-clotting ability, ie, inhibition of platelet aggregation, by these medications and/or plicamycin combined with induction of hypoprothrombinemia by plicamycin and large dose of aspirin; in addition, the gastrointestinal ulcerative or hemorrhagic potential of aspirin, the nonsteroidal anti-inflammatory drugs, or sulfinpyrazone may increase the risk of hemorrhage in plicamycin-treated patients.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

同时使用其他骨髓抑制药、肝毒性药物或肾毒性药物可能会增加中毒的风险。

Concurrent use /of other bone marrow depressants, hepatotoxic medications, or nephrotoxic medications/ may increase the potential for toxicity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

维生素D的并发使用，包括钙化二醇和钙三醇，可能会在使用作为钙通道拮抗剂时抵消plicamycin的效果。

Concurrent use /of vitamin D, including calcifediol and calcitriol/ may antagonize the effect of plicamycin when used as a calcium antagonist.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

不知道plicamycin是否会分泌在母乳中。

It is not known whether plicamycin is excreted in breast milk.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

作用持续时间：单次给药后7至10天。

Duration of action: 7 to 10 days with a single dose.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

效果达到峰值的时间：单次剂量后72小时。

Time to peak effect: 72 hours with a single dose.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

作用开始时间：用于治疗高钙血症时，通常在给药后24至48小时内血浆钙含量会降低。

Onset of action: When used for hypercalcemia, a reduction in plasma calcium usually occurs within 24 to 48 hours following administration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

plicamycin在肝脏的库普弗细胞、肾小管细胞和形成的骨表面中浓缩。它可能定位于活跃的骨吸收区域。Plicamycin还穿过血脑屏障，进入脑脊液（CSF）。

Plicamycin is concentrated in the Kupffer cells of the liver, in renal tubular cells, and along formed bone surfaces. It may localize in areas of active bone resorption. Plicamycin also crosses the blood-brain barrier and enters the cerebrospinal fluid (CSF).

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• COMPOUNDS FOR THE TREATMENT OF RENAL CELL CARCINOMA
  申请人：Maher Eamonn

  公开号：US20130150317A1

  公开（公告）日：2013-06-13

  A composition comprising mithramycin or a pharmaceutically acceptable salt or solvate thereof for use in the treatment of renal cell carcinoma. In particular, the composition is suitable for use in the treatment of clear cell renal cell carcinoma. The composition is particularly useful for use in the treatment of renal cell carcinoma associated with Von Hippel-Lindau disease or Birt-Hogg-Dubé syndrome. A composition comprising mithramycin or a pharmaceutically acceptable salt or solvate thereof for use as a cytotoxic agent against FLCN-null or VHL-null renal cell carcinoma cells.