CCL-44

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: CCL-44
• 英文别名: N-[(2S)-1-oxo-3-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1-(undecylamino)propan-2-yl]octadecanamide
• 化学式: C₃₈H₇₄N₂O₈
• 分子量: 687.014
• InChiKey: NGHPPMHYFFODQL-DQPDPZHXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.1
• 重原子数：
  48
• 可旋转键数：
  32
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  158
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 CCL-44
  参考文献：
  名称：

  A synthetic analog of α-galactosylceramide induces macrophage activation via the TLR4-signaling pathways

  摘要：

  a-Galactosylceramide (a-GalCer), a bioactive glycolipid isolated from the marine sponge Agelas mauritianus, is a potent immunomodulator with therapeutic potential for the treatment of autoimmune diseases and cancer. The Toll-like receptor 4 (TLR4:), one of the promising molecular targets for immune-modulating drugs, is commonly expressed in innate immune cells especially macrophages and dendritic cells. Currently, whether alpha-GalCer can activate TLR4 signaling pathways remains unreported. In this study, we examined the effects of alpha-GalCer and its various structural analogs, CCL-1 similar to 47, on TLR4 activation. We found that one a-GalCer analog (CCL-34), but not a-GalCer itself, strongly stimulated NF-kappa B activity in RAW 264.7 cells. CCL-34 activated NF-kappa B in a TLR4-dependent manner and stimulated TNF-alpha production in bone marrow cells of TLR4-functional C3H/HeN mice but not in those of TLR4-defective C3H/HeJ mice. Furthermore, CCL-34 treatment stimulated NF-kappa B activation and IL-8 production in a 293 cell line constitutively expressing human TLR4, MD-2 and CD14. Treatment of RAW 264.7 cells with CCL-34 also activated TLR4-downstream mitogen-activated protein kinases (ERK, JNK and p38), induced expression of TLR4-downstream genes (TNF-alpha, IL-6, IL-1 beta and iNOS) and promoted production of cytokines characteristic of activated macrophages. CCL-34-treated RAW 264.7 cells acquired a distinct morphology similar to that of LPS-activated macrophages and exhibited higher phagocytotic activity. Moreover, treatment with a TLR4-neutalizing antibody inhibited the CCL-34-induced morphological alteration. In summary, we identify a novel synthetic compound CCL-34 that can activate macrophages via TLR4-dependent signaling pathways. Our results suggest that CCL-34 is an immune modulator and may serve as a potential drug lead for immunotherapy. (c) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2007.03.006

文献信息

• A synthetic analog of α-galactosylceramide induces macrophage activation via the TLR4-signaling pathways
  作者：Ling-Chien Hung、Chun-Cheng Lin、Shih-Kai Hung、Bing-Ching Wu、Mi-Dan Jan、Sheng-Hung Liou、Shu-Ling Fu

  DOI：10.1016/j.bcp.2007.03.006

  日期：2007.6

  a-Galactosylceramide (a-GalCer), a bioactive glycolipid isolated from the marine sponge Agelas mauritianus, is a potent immunomodulator with therapeutic potential for the treatment of autoimmune diseases and cancer. The Toll-like receptor 4 (TLR4:), one of the promising molecular targets for immune-modulating drugs, is commonly expressed in innate immune cells especially macrophages and dendritic cells. Currently, whether alpha-GalCer can activate TLR4 signaling pathways remains unreported. In this study, we examined the effects of alpha-GalCer and its various structural analogs, CCL-1 similar to 47, on TLR4 activation. We found that one a-GalCer analog (CCL-34), but not a-GalCer itself, strongly stimulated NF-kappa B activity in RAW 264.7 cells. CCL-34 activated NF-kappa B in a TLR4-dependent manner and stimulated TNF-alpha production in bone marrow cells of TLR4-functional C3H/HeN mice but not in those of TLR4-defective C3H/HeJ mice. Furthermore, CCL-34 treatment stimulated NF-kappa B activation and IL-8 production in a 293 cell line constitutively expressing human TLR4, MD-2 and CD14. Treatment of RAW 264.7 cells with CCL-34 also activated TLR4-downstream mitogen-activated protein kinases (ERK, JNK and p38), induced expression of TLR4-downstream genes (TNF-alpha, IL-6, IL-1 beta and iNOS) and promoted production of cytokines characteristic of activated macrophages. CCL-34-treated RAW 264.7 cells acquired a distinct morphology similar to that of LPS-activated macrophages and exhibited higher phagocytotic activity. Moreover, treatment with a TLR4-neutalizing antibody inhibited the CCL-34-induced morphological alteration. In summary, we identify a novel synthetic compound CCL-34 that can activate macrophages via TLR4-dependent signaling pathways. Our results suggest that CCL-34 is an immune modulator and may serve as a potential drug lead for immunotherapy. (c) 2007 Elsevier Inc. All rights reserved.