NAMI-A – The Iconic Non-Cytotoxic Ruthenium Agent Targeting Tumor Metastases: Comprehensive Overview
NAMI-A (imidazolium trans-[tetrachloro(dimethylsulfoxide)(imidazole)ruthenate (III)]) is one of the well-investigated ruthenium-based anti-cancer compounds. Contrary to the classical platinum compounds, NAMI-A revealed low cytotoxicity towards primary tumours but selective antimetastatic properties in various preclinical models. Due to its distinct pharmacological properties, including rapid ligand exchange, protein and extracellular matrix interactions, tumour microenvironment modulation, and anti-angiogenic properties, NAMI-A entered clinical development in combination with gemcitabine. These clinical findings revealed limited efficacy and biologic tolerance with attendant restrictions for further development of NAMI-A as a systemic antimetastatic agent for cancer therapy, despite NAMI-A remaining a prototype for research in the development of new metallodrugs with antimetastatic properties. This review focuses on the various properties of NAMI-A, including its biochemistry, mechanism of action, preclinical and clinical data, structure-activity relationship, formulations/form pharmacokinetics, combination development, and future directions for development of next-generation compounds for therapeutic applications with antimetastatic therapies.