(2S,3S)-2-[(2S,4R,5R,6R)-4-[(2S,4R,5R,6R)-4-[(2S,4S,5R,6R)-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-[(2S,4R,5R,6R)-4-[(2S,4R,5S,6R)-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,3S)-2-[(2S,4R,5R,6R)-4-[(2S,4R,5R,6R)-4-[(2S,4S,5R,6R)-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-[(2S,4R,5R,6R)-4-[(2S,4R,5S,6R)-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-WZIVUMCRSA-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

• 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的同时使用，包括钙化二醇和钙三醇，可能会拮抗plicamycin作为钙通道阻滞剂时的效果。

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)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，如有需要，进行辅助通气。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预防癫痫发作，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

不知道是否在乳汁中排泄吡咯酸。

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

首次给药后72小时达到最大效果。

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

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

起效时间：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

• ANTIBODIES
  申请人：Sathyanarayanan Sriram

  公开号：US20120058112A1

  公开（公告）日：2012-03-08

  The combination of an IGF-1R antagonist such as a humanized antibody and an anti-proliferative drug is described. In a preferred embodiment, the present invention describes the combination of an IGF-1R antibody and an anti-proliferative drug belonging to the EGFR-inhibitor class, which is preferably erlotinib. The combination according to the present invention is useful for the treatment of tumours, including IGF-1R and/or EGFR mediated or dependent tumours.

  本发明描述了IGF-1R拮抗剂（例如人源化抗体）和抗增殖药物的组合。在一种优选实施方案中，本发明描述了IGF-1R抗体和属于EGFR抑制剂类的抗增殖药物（优选为厄洛替尼）的组合。根据本发明的组合对于治疗肿瘤，包括IGF-1R和/或EGFR介导或依赖的肿瘤是有用的。
• BIOMARKERS FOR SENSITIVITY TO ANTI-IGF1R THERAPY
  申请人：Wang Yan

  公开号：US20110091524A1

  公开（公告）日：2011-04-21

  The present invention provides, for example, methods for conveniently determining if a cancerous condition in a subject will be responsive to an IGF1R inhibitor. The invention includes patient selection methods and methods of treatment.

  本发明提供了方便确定受试者的癌症状况是否对IGF1R抑制剂具有响应的方法。该发明包括患者选择方法和治疗方法。
• METHODS OF TREATMENT
  申请人：Wang Yan

  公开号：US20110262525A1

  公开（公告）日：2011-10-27

  This invention relates to compositions and methods useful for treating various cancers. Therapeutic combinations and methods of use thereof are also covered in the present application.

  本发明涉及用于治疗各种癌症的组合物和方法。本申请还涵盖了治疗组合物和使用方法。
• FDG-PET EVALUATION OF EWING'S SARCOMA SENSITIVITY
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20130243692A1

  公开（公告）日：2013-09-19

  This invention relates to methods for evaluating the efficacy of an IGF1R inhibitor, such as an anti-IGF1R antibody, for the treatment of an Ewing's sarcoma tumor by determining the level of tumoral glucose metabolism. Tumoral glucose metabolism is determining at an early point in the treatment regimen by any of several methods known in the art including FDG-PET/CT scan.

  本发明涉及一种评估IGF1R抑制剂（如抗IGF1R抗体）对Ewing肉瘤肿瘤治疗疗效的方法，通过确定肿瘤葡萄糖代谢水平来进行。肿瘤葡萄糖代谢可以通过艺术中已知的几种方法之一（包括FDG-PET/CT扫描）在治疗方案的早期阶段进行确定。
• ANTI-IGF1R
  申请人：Wang Yan

  公开号：US20110014117A1

  公开（公告）日：2011-01-20

  The present invention relates in part to anti-IGF1R antibodies and antigen-binding compositions thereof along with methods of use thereof. For example, methods of treating medical disorders such as cancer are covered.

  本发明部分涉及抗IGF1R抗体及其抗原结合组成物，以及其使用方法。例如，涵盖了治疗癌症等医学疾病的方法。