Docking-Guided Discovery of Neuromodulatory Agents for Brain Cancer

High-grade gliomas exploit neural circuits to support growth, creating neuromodulatory vulnerabilities amenable to pharmacological targeting. This chapter presents a practical pipeline that centers on molecular docking and complementary in-silico methods to discover and prioritize neuromodulatory compounds for brain cancer. We summarize neuron-glioma signaling targets (glutamatergic/GABAergic receptors, synaptogenic proteins, ion channels), outline virtual screening and flexible docking approaches, and describe follow-up stability assessments with molecular dynamics (MD), artificial intelligence/machine learning (AI/ML) prioritization, and network-pharmacology mapping. Representative examples, such as perampanel, gabapentin, and valproic acid, illustrate opportunities and translational barriers, particularly blood–brain barrier penetration, protein flexibility, and scoring limitations. Finally, we propose experimental validation paths and delivery strategies, such as focused ultrasound and nanoparticle systems, to bridge computational predictions and clinical translation. Emphasizing rigorous docking methodology and integrated validation will accelerate the repurposing and discovery of neuromodulatory agents for brain cancer.