FK506 | 104987-11-3

• 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 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: FK506
• 英文别名: (1R,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone
• CAS: 104987-11-3；129212-35-7；135635-56-2；144490-63-1
• 化学式: C₄₄H₆₉NO₁₂
• 分子量: 804.031
• InChiKey: QJJXYPPXXYFBGM-RGMZVGHXSA-N

物化性质

• 熔点：
  113-115°C
• 沸点：
  871.7±75.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)
• 闪点：
  2℃
• 溶解度：
  二甲基亚砜：>3 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  57
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  178
• 氢给体数：
  3
• 氢受体数：
  12

安全信息

• 危险等级：
  6.1
• 危险品标志：
  Xi,T
• 安全说明：
  S26,S36,S45
• 危险类别码：
  R36/37/38,R25
• WGK Germany：
  3
• 海关编码：
  29349990
• 危险品运输编号：
  UN 2811 6.1/PG 3
• RTECS号：
  KD4201200
• 危险类别：
  6.1
• 包装等级：
  III
• 危险性防范说明：
  P264,P270,P301+P310+P330,P405,P501
• 危险性描述：
  H301

制备方法与用途

他克莫司是一种大环内酯类免疫抑制剂,主要通过以下机制发挥作用:

1. 与FK506结合蛋白(FKBP)形成复合体。

2. 降低T细胞中肽酰脯氨酰异构酶活性。

3. 抑制白细胞介素-2的合成。

4. 主要用于预防器官移植后的排异反应,对急性排异反应疗效更佳。

他克莫司的生产工艺如下:

1. 发酵生产:从Streptomyces tsukubaensis菌种发酵得到。

2. 提取分离:将发酵液过滤后用丙酮提取,通过树脂柱层析纯化。

3. 净化:经过硅胶色谱和反相高效液相色谱进一步纯化。

4. 结晶:浓缩溶液重结晶得到无色棱状结晶的纯品。

他克莫司的主要用途:

1. 器官移植后预防排异反应

2. 治疗某些自身免疫性疾病,如肾炎、视网膜炎等

需要注意的是,他克莫司是一种处方药,需在医生指导下使用。由于其较强的免疫抑制作用,可能存在感染风险和肾毒性等不良反应。

文献信息

• MODIFIED DRUGS FOR USE IN LIPOSOMAL NANOPARTICLES
  申请人：THE UNIVERSITY OF BRITISH COLUMBIA

  公开号：US20180221279A1

  公开（公告）日：2018-08-09

  Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

  本文提供了适用于装载到脂质体纳米粒载体中的药物衍生物。在一些首选方面，这些衍生物包括一种水溶性较差的药物衍生物，其与一种弱碱基团衍生化，有助于通过LN跨膜pH或离子梯度将药物活性地装载到LN的水相内部。弱碱基团可以选择性地包括一个亲脂性结构域，有助于将药物活性地装载到脂质体膜的内单分子层。优点是，药物衍生物的LN配方相对于相应的游离药物表现出改善的溶解度、降低的毒性、增强的疗效和/或其他优点。
• NOVEL TACROLIMUS ANALOGUES, A NEUROPROTECTIVE COMPOSITION COMPRISING THE SAME, AN IMMUNOSUPPRESSIVE COMPOSITION COMPRISING THE SAME, A METHOD FOR PREPARING THE SAME, AND A MUTANT FOR PRODUCING THE SAME
  申请人：EWHA UNIVERSITY- INDUSTRY COLLABORATION FOUNDATION

  公开号：US20130230559A1

  公开（公告）日：2013-09-05

  The present invention relates to novel tacrolimus analogues, a composition for the prevention or treatment of neurological diseases or immune hypersensitivity disorders comprising the same, a method for preventing or treating neurological diseases or immune hypersensitivity disorders comprising administering the analogues to a subject, a method for preparing the analogues using an isolated modified Streptomyces sp. strain wherein the activity of one or more enzymes selected from the group consisting of TcsA, TcsB, TcsC and TcsD is reduced; and the isolated modified Streptomyces sp. strain for prepare the analogues.

  本发明涉及新型他克莫司类似物，一种用于预防或治疗神经疾病或免疫过敏性疾病的组合物，包括相同的组成部分，一种通过向受试者施用类似物来预防或治疗神经疾病或免疫过敏性疾病的方法，一种使用经过改良的分离链霉菌菌株制备类似物的方法，其中来自于TcsA、TcsB、TcsC和TcsD组中选择的一个或多个酶的活性被降低；以及用于制备类似物的经过改良的分离链霉菌菌株。
• Modified Drugs for Use in Liposomal Nanoparticles
  申请人：Cullis Peter

  公开号：US20110165225A1

  公开（公告）日：2011-07-07

  Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

  本文提供了适用于载入脂质体纳米粒子载体的拖曳导数。在某些优选方面，这些导数包括一种难溶于水的拖曳经过弱碱基团衍生化，该弱碱基团促进通过LN跨膜pH或离子梯度将拖曳活性负载到LN的水内部。弱碱基团可以选择包括一个亲脂性域，该亲脂性域促进将拖曳活性负载到脂质体膜的内单层。优点是，与相应的自由拖曳相比，拖曳导数的LN配方表现出改善的溶解度、降低的毒性、增强的功效和/或其他益处。
• Tacrolimus Standard and Methods of Using Same
  申请人：Wei Tie Q.

  公开号：US20100062459A1

  公开（公告）日：2010-03-11

  A composition and kit useful as a tacrolimus standard solution for immunoassays, and methods for making and using same. The composition and kits include a known amount of tacrolimus or a derivative thereof, and a non-specific protein capable of forming a complex with the tacrolimus or derivative thereof. The standard solution may be used to generate calibration curves for an immunoassay or to check the precision of an analytical instrument.
• TACROLIMUS COMPOSITIONS FOR AEROSOL ADMINISTRATION
  申请人：Dalby Richard N.

  公开号：US20110318277A1

  公开（公告）日：2011-12-29

  The present disclosure relates generally to highly concentrated macrolide solutions for aerosol administration, and related methods of producing and administering the same. In one aspect, provided herein is a receptacle containing a highly concentrated solution of a macrolide compound such as tacrolimus, where the solution exhibits long-term stability in a pMDI canister and achieves high respirable fractions when actuated, among, other features. In yet another aspect, provided is a composition suitable for aerosol administration comprising tacrolimus dissolved in an ethanol-liquified propellant mixture, characterized by a tacrolimus concentration of greater than 0.15 weight percent (w/w) and comprising no more than about 10 weight percent (w/w) ethanol.