1区 · 医学
Article
作者: Rao, Jinlong ; Zhang, Xuan ; Zheng, Purong ; Yan, Jie ; Ou, Yingye ; Bei, Xuelu ; Li, Shuo ; Wu, Weibin ; Ma, Yao ; Hu, Chunyun ; Huang, Weixin ; Pan, Tingting ; Wan, Long ; Wen, Xiaoming ; Wu, Ningbin ; Jin, Jian ; Li, Hongzu ; Liu, Shoujia ; Wang, Ziyu ; Cai, Youyou ; Liu, Gang ; Zhang, Qianli ; Lin, Ruwen ; Cheng, Wenming
Salutaxel (3) is a conjugate of docetaxel (7) and a muramyl dipeptide (MDP) analogue. Docetaxel (7) has been recognized as a highly active chemotherapeutic agent against various cancers. MDP and its analogues are powerful potentiators of the antitumor actions of various tumor-necrotizing agents. This article documents the discovery of compound 3 and presents pharmacological proof of its biological function in tumor-bearing mice. Drug candidate 3 was superior to compound 7 in its ability to prevent tumor growth and metastasis. Compound 3 suppressed myeloid-derived suppressor cell (MDSC) accumulation in the spleens of tumor-bearing mice and decreased various serum inflammatory cytokines levels. Furthermore, compound 3 antagonized the nucleotide-binding oligomerization domain-like receptor 1 (NOD1) signaling pathway both in vitro and in vivo.