Salutaxel, a Conjugate of Docetaxel and a Muramyl Dipeptide (MDP) Analogue, Acts as Multifunctional Prodrug That Inhibits Tumor Growth and Metastasis

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.