methotrexate N-hydroxysuccinimde ester | 122856-33-1

• 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: methotrexate N-hydroxysuccinimde ester
• 英文别名: MTX-NHS；Aminopterin N-hydroxysuccinimide ester；(2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]-5-(2,5-dioxopyrrolidin-1-yl)oxy-5-oxopentanoic acid
• CAS: 122856-33-1
• 化学式: C₂₄H₂₅N₉O₇
• 分子量: 551.519
• InChiKey: MYDJRYXFBSZFTR-HNNXBMFYSA-N

物化性质

• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  237
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  methotrexate N-hydroxysuccinimde ester 、 glycine-phenylananine-leucine-glycine 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 以78%的产率得到methotrexate-GFLG
  参考文献：
  名称：

  Arabinogalactan−Folic Acid−Drug Conjugate for Targeted Delivery and Target-Activated Release of Anticancer Drugs to Folate Receptor-Overexpressing Cells

  摘要：

  Folic acid (FA) is a high affinity ligand (K(d) = 0.1-1 nM) of folate receptors (FRs) responsible for cellular uptake of folates via receptor-mediated endocytosis. FRs are frequently overexpressed in malignant epithelial cells including ovary, brain, kidney, breast, colon, and lung. FR has emerged as a target for the differential-delivery of anticancer chemotherapeutics with several FA-linked therapeutic agents currently undergoing clinical trials. Here we show that by tethering both FA and the anticancer drug methotrexate (MTX) to arabinogalactan (AG), a highly branched natural polysaccharide with unusual water solubility, a targeted biomacromolecular nanovehicle is formed, which can differentially deliver a cytotoxic cargo into FR-overexpressing cells. Moreover, by linking MTX via an endosomally cleavable peptide (GFLG), we demonstrate target-activated release mechanism. This FA-AG-GFLG-MTX drug conjugate displayed 6.3-fold increased cytotoxic activity to FR-overexpressing cells compared to their FR-lacking counterparts. These findings establish a novel FA-tethered polymeric nanoconjugate for the targeted delivery of antitumor agents into cancer cells overexpressing FR.

  DOI：

  10.1021/bm900853z
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 甲氨蝶呤 在 吡啶 、 N,N'-二环己基碳二亚胺 作用下， 反应 24.0h， 生成 methotrexate N-hydroxysuccinimde ester
  参考文献：
  名称：

  吉西他滨和甲氨蝶呤的大分子双药促进肿瘤特异性双重药物治疗，具有更高的风险比

  摘要：

  本研究报告了通过将两种不同的抗癌剂即吉西他滨（GEM）和甲氨蝶呤（MTX）附加到长循环聚（）的末端而合成的新型大分子双药丸的合成，表征和生物学评估。 （乙二醇）（PEG）间隔基。GEM和MTX通过PEG接头的共价偶联不仅改变了组成药物分子的溶解度，而且显着提高了它们在血浆中的稳定性。在体外细胞毒性研究证实，GEM-PEG-MTX发挥更高的细胞毒性（IC 50 0.181μM在24小时），在人乳腺癌MCF-7细胞系中，当相比于游离药物同类物，即游离GEM（IC 50 0.294μM在24小时）和免费的MTX（IC 50在24 h时为0.591μM）。在化学诱导的荷瘤大鼠中进行的肿瘤生长抑制研究确立了GEM-PEG-MTX缀合物优于所有其他药物制剂的优势，包括游离药物，GEM和MTX的物理混合物以及聚乙二醇化的GEM / MTX。在荷瘤大鼠和健康小鼠中进行的毒性研究证实，双重药物结合是在减轻与

  DOI：

  10.1021/bc400477q

文献信息

• Alginate stabilized gold nanoparticle as multidrug carrier: Evaluation of cellular interactions and hemolytic potential
  作者：Soma Dey、M. Caroline Diana Sherly、M.R. Rekha、K. Sreenivasan

  DOI：10.1016/j.carbpol.2015.09.016

  日期：2016.1

  This work delineates the synthesis of curcumin (Ccm) and methotrexate (MTX) conjugated biopolymer stabilized AuNPs (MP@Alg-Ccm AuNPs). The dual drug conjugated nano-vector was characterized by FTIR, 1H NMR and UV-vis spectroscopic techniques. Hydrodynamic diameter and surface charge of the AuNPs were determined by DLS analysis and the spherical particles were visualized by TEM. MP@Alg-Ccm AuNPs exhibited improved cytotoxic potential against C6 glioma and MCF-7 cancer cell lines and was found to be highly hemocompatible. MP@Alg-Ccm AuNPs also exhibited active targeting efficiency against MCF-7 cancer cells due to the presence of "antifolate" drug MTX. Thus MP@Alg-Ccm AuNPs may find potential application in targeted combination chemotherapy for the treatment of cancer. The study is also interesting from the synthetic point of view because, here generation of AuNPs was done using "green chemical" alginate and dual drug conjugated AuNPs were created in two simple reaction steps using "green solvent" water. (C) 2015 Elsevier Ltd. All rights reserved.
• Arabinogalactan−Folic Acid−Drug Conjugate for Targeted Delivery and Target-Activated Release of Anticancer Drugs to Folate Receptor-Overexpressing Cells
  作者：Roy I. Pinhassi、Yehuda G. Assaraf、Shimon Farber、Michal Stark、Diana Ickowicz、Stavit Drori、Abraham J. Domb、Yoav D. Livney

  DOI：10.1021/bm900853z

  日期：2010.1.11

  Folic acid (FA) is a high affinity ligand (K(d) = 0.1-1 nM) of folate receptors (FRs) responsible for cellular uptake of folates via receptor-mediated endocytosis. FRs are frequently overexpressed in malignant epithelial cells including ovary, brain, kidney, breast, colon, and lung. FR has emerged as a target for the differential-delivery of anticancer chemotherapeutics with several FA-linked therapeutic agents currently undergoing clinical trials. Here we show that by tethering both FA and the anticancer drug methotrexate (MTX) to arabinogalactan (AG), a highly branched natural polysaccharide with unusual water solubility, a targeted biomacromolecular nanovehicle is formed, which can differentially deliver a cytotoxic cargo into FR-overexpressing cells. Moreover, by linking MTX via an endosomally cleavable peptide (GFLG), we demonstrate target-activated release mechanism. This FA-AG-GFLG-MTX drug conjugate displayed 6.3-fold increased cytotoxic activity to FR-overexpressing cells compared to their FR-lacking counterparts. These findings establish a novel FA-tethered polymeric nanoconjugate for the targeted delivery of antitumor agents into cancer cells overexpressing FR.
• Macromolecular Bipill of Gemcitabine and Methotrexate Facilitates Tumor-Specific Dual Drug Therapy with Higher Benefit-to-Risk Ratio
  作者：Manasmita Das、Roopal Jain、Ashish Kumar Agrawal、Kaushik Thanki、Sanyog Jain

  DOI：10.1021/bc400477q

  日期：2014.3.19

  The present study reports the synthesis, characterization, and biological evaluation of a novel macromolecular bipill, synthesized by appending two different anticancer agents, viz., gemcitabine (GEM) and methotrexate (MTX), to the distal ends of a long-circulating poly(ethylene glycol) (PEG) spacer. Covalent conjugation of GEM and MTX via PEG linker not only transformed the solubility profiles of

  本研究报告了通过将两种不同的抗癌剂即吉西他滨（GEM）和甲氨蝶呤（MTX）附加到长循环聚（）的末端而合成的新型大分子双药丸的合成，表征和生物学评估。 （乙二醇）（PEG）间隔基。GEM和MTX通过PEG接头的共价偶联不仅改变了组成药物分子的溶解度，而且显着提高了它们在血浆中的稳定性。在体外细胞毒性研究证实，GEM-PEG-MTX发挥更高的细胞毒性（IC 50 0.181μM在24小时），在人乳腺癌MCF-7细胞系中，当相比于游离药物同类物，即游离GEM（IC 50 0.294μM在24小时）和免费的MTX（IC 50在24 h时为0.591μM）。在化学诱导的荷瘤大鼠中进行的肿瘤生长抑制研究确立了GEM-PEG-MTX缀合物优于所有其他药物制剂的优势，包括游离药物，GEM和MTX的物理混合物以及聚乙二醇化的GEM / MTX。在荷瘤大鼠和健康小鼠中进行的毒性研究证实，双重药物结合是在减轻与