title: Antagonizing NOD2 Signaling with Conjugates of Paclitaxel and Muramyl Dipeptide Derivatives Sensitizes Paclitaxel Therapy and Significantly Prevents Tumor Metastasis.
abstract: A noncleavable paclitaxel (PTX) and N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) derivative conjugate, 22 (DY-16-43), and its analogues were prepared and characterized as antagonists of NOD2 signaling. This conjugate enhanced the antitumor and antimetastatic efficacy of PTX in Lewis lung carcinoma (LLC) tumor-bearing mice. This work first describes a molecular strategy that enables the sensitization of a chemotherapeutic response via antagonizing NOD2 inflammatory signaling and suggests NOD2 antagonist as potential adjunct in treating non-small-cell lung cancer (NSCLC).
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua University , Haidian District, Beijing 100084, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , 2A Nanwei Road, Xicheng District, Beijing 100050, P. R. China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua University , Haidian District, Beijing 100084, P. R. China.
authors.forename: Chunting
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua University , Haidian District, Beijing 100084, P. R. China.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua University , Haidian District, Beijing 100084, P. R. China.|Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , 2A Nanwei Road, Xicheng District, Beijing 100050, P. R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Pharmaceutical Sciences, Tsinghua University , Haidian District, Beijing 100084, P. R. China.
authors.forename: Gang
authors.identifier: 0000-0001-5549-5686
authors.initials: G
authors.lastname: Liu
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D004357:Drug Synergism; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D017239:Paclitaxel