benzoxazine-derived compound

The benzoxazine-derived compound is a novel, orally bioavailable small molecule developed by the University of Granada (Grupo de Investigación CTS-963) that targets cancer stem cells (CSCs) in pancreatic cancer. Synthesized via a one-step halogenation process, the compound exhibits submicromolar potency in pancreatic CSC-enriched models, outperforming salinomycin with improved solubility and a favorable toxicity profile. It selectively depletes CSC populations, induces apoptosis and cell cycle arrest, and downregulates key CSC markers (including CD44v6, mesothelin, MUC1, CEACAM19, L1CAM, and CD105). Transcriptomic profiling indicates that the compound inhibits oncogenic pathways such as ERBB2/ERBB4, MAPK, and VEGF, as well as transcription factors SOX2, KLF4, and E2F4. In preclinical patient-derived pancreatic cancer (PDX) models, the compound demonstrated oral bioavailability, favorable pharmacokinetics, and good tolerability, significantly delaying tumor initiation and suppressing tumor growth.