Conjugate (MTC-220) of muramyl dipeptide analogue and paclitaxel prevents both tumor growth and metastasis in mice

J Med Chem. 2011 Apr 28;54(8):2767-77. doi: 10.1021/jm101577z. Epub 2011 Mar 15.

Abstract

1 (MTC-220), a conjugate of paclitaxel and a muramyl dipeptide analogue, has been synthesized as a novel agent of dual antitumor growth and metastasis activities. In vitro and in vivo tests show that 1 retains its ability to inhibit tumor growth. It is superior to paclitaxel in its ability to prevent tumor metastasis in Lewis lung carcinoma and 4T1-tumor-bearing mice. The present studies indicate that 1 suppresses myeloid derived suppressor cell accumulation in the spleen and bone marrow of tumor-bearing mice and also represses inflammatory cytokines in tumor tissue. These results demonstrated that 1 could be a potential therapeutic and preventive agent for cancer growth and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology*
  • Animals
  • Bone Marrow Cells / drug effects
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma, Lewis Lung / pathology*
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Cytokines / metabolism
  • Dipeptides / pharmacology*
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis / prevention & control*
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / pharmacology*

Substances

  • Cytokines
  • Dipeptides
  • Inflammation Mediators
  • MTC-220
  • Acetylmuramyl-Alanyl-Isoglutamine
  • Paclitaxel