Sartans and Bisartans: Expanding Therapeutic Horizons Through Broad Receptor Interactions and Repurposing Potential.

Angiotensin receptor blockers (ARBs), also known as sartans, are a family of highly selective angiotensin II type 1 receptor antagonists commonly prescribed to individuals with hypertension, heart failure, and chronic kidney disease. Additionally, the discovery and facile synthesis of bisartans, a novel class of ARB antihypertensives, have shown therapeutic promise for cardiovascular diseases. Recent computational and network pharmacology studies have shown a broader receptor interactome, encompassing alpha-adrenergic receptors, and delta- and mu-opioid receptors, highlighting the polypharmacology of ARBs. Herein, we combine molecular docking, molecular dynamics, and protein-protein interaction analyses to characterize the binding profiles of sartans and bisartans, as well as conformational impacts across multiple G-protein-coupled receptors. Emphasis is placed on their potential to modulate receptor desensitization states and influence pathways involved in neuropsychiatric disorders, addiction, viral infections, and cardiovascular diseases. Limitations of current computational approaches are discussed alongside the need for experimental proteomic validation. Collectively, this evidence positions sartans and bisartans as structurally privileged scaffolds for multi-target drug repurposing and precision medicine applications.