demomedin C | 1400304-52-0

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: demomedin C
• 英文别名: (2S)-2-[[2-[[3-(2-aminoethylamino)-2-[(2-aminoethylamino)methyl]propanoyl]amino]acetyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]butanediamide
• CAS: 1400304-52-0
• 化学式: C₅₈H₉₁N₂₁O₁₂S
• 分子量: 1306.56
• InChiKey: HAAVNIFDWNLVDH-WKJJQBNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.3
• 重原子数：
  92
• 可旋转键数：
  43
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  552
• 氢给体数：
  19
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  N,N′,N″,N‴-tetrakis-(tert-butoxycarbonyl)-6-(carboxy)-1,4,8,11-tetraazaundecane 在 茴香硫醚 、 三氟乙酸 作用下， 以 水 为溶剂， 反应 0.5h， 生成 demomedin C
  参考文献：
  名称：

  [^99mTc]Demomedin C, a Radioligand Based on Human Gastrin Releasing Peptide(18-27): Synthesis and Preclinical Evaluation in Gastrin Releasing Peptide Receptor-Expressing Models

  摘要：

  The synthesis and preclinical evaluation of [Tc-99m]Demomedin C in GRPR-expressing models are reported. Demomedin C resulted by coupling a Boc-protected N-4-chelator to neuromedin C (human GRP(18-27)), which, after Tc-99m-labeling, afforded [Tc-99m]Demomedin C. Demomedin C showed high affinity and selectivity for the GRPR during receptor autoradiography on human cancer samples (IC50 in nM: GRPR, 1.4 +/- 0.2; NMBR, 106 +/- 18; and BB3R, >1000). It triggered GRPR internalization in HEK-GRPR cells and Ca2+ release in PC-3 cells (EC50 = 1.3 nM). [Tc-99m]Demomedin C rapidly and specifically internalized at 37 degrees C in PC-3 cells and was stable in mouse plasma. [Tc-99m]Demomedin C efficiently and specifically localized in human PC-3 implants in mice (9.84 +/- 0.81%ID/g at 1 h pi; 6.36 +/- 0.8596ID/g at 4 h pi, and 0.41 +/- 0.07%ID/g at 4 h pi block). Thus, human GRP-based radioligands, such as [Tc-99m]Demomedin C, can successfully target GRPR-expressing human tumors in vivo while displaying attractive biological features-e.g. higher GRPR-selectivity-vs their frog-homologues.

  DOI：

  10.1021/jm300741f