Exploring Pyridazine Pharmacophores for the Development of Novel Therapeutics Against Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a highly aggressive and diverse form of breast cancer characterized by the absence of progesterone and Estrogen receptors and HER2 expression, which limits conventional therapeutic options and contributes to poor prognosis. Chemotherapy remains the standard of care, but multidrug resistance, tumor heterogeneity, and systemic toxicities restrict long-term efficacy. Recent advances focus on pyridazine-based derivatives, whose heteroaromatic scaffolds enable selective targeting of receptor tyrosine kinases, apoptosis regulators, and oncogenic pathways. Structural modifications, including halogenation and hybridization with pyrazoline, triazole, or pyridazine moieties, enhance potency, metabolic stability, and multi-targeted activity. Multifunctional molecular probes (MMPs) further enable tumor-specific drug delivery, real-time imaging, and theragnostic applications through ligand-conjugated nanocarriers and advanced modalities such as MRI, near-infrared fluorescence, and radionuclide imaging. Integration of computational tools, molecular docking, and artificial intelligence accelerates rational drug design and optimization, while patented platforms provide translational frameworks for clinical development. Collectively, the convergence of pyridazine derivatives, MMPs, and computational-guided strategies promises precision-targeted, adaptive therapies capable of overcoming resistance, reducing systemic toxicity, and improving outcomes in TNBC.