Somatostatin Receptors as a Target for the Treatment of High-Risk Neuroblastoma Stage 4 (NBS4)

Somatostatin receptors are being investigated as therapeutic targets for high‑risk neuroblastoma stage 4 (NBS4) due to their overexpression on chromosome 17q. This study explores the design of potential somatostatin receptor agonists that activate SSTR2 signalling pathways. It evaluates their ability to bind two additional overexpressed GPCRs located on chromosome 17: galanin receptor type 2 (GALR2) and corticotropin‑releasing hormone receptor 1 (CRHR1). Using a multi‑platform computer‑aided drug design workflow—including OpenEye Scientific Suite, Samson Suite, Flare Suite, and Discovery Studio Visualizer—eight candidate compounds were identified and assessed for docking performance, pose reliability, and structure–activity relationship (SAR). Their absorption, distribution, metabolism, excretion, and toxicity profiles were evaluated using T.E.S.T., DEEP‑PK, and SwissADME. Retrosynthetic analysis using ChemAIRS and Spaya confirmed synthetic feasibility, with compound 8 achieving an RScore of 1.0. Compound 8 demonstrated strong and consistent predicted binding to SSTR2, CRHR1, and GALR2, with interaction patterns consistent with those reported for known SSTR2 agonists. These findings suggest that compound 8 is a promising multitarget GPCR ligand candidate for high-risk NBS4 and warrants further experimental evaluation of its pharmacological activity.