PROTAC-Surufatinib Suppresses Pancreatic Neuroendocrine Neoplasms Progression by Inducing Ferroptosis through Inhibiting WNT/β-catenin Pathway Mediated by HMOX1.

ABSTRACT: The small-molecule targeting drug Surufatinib is a new strategy for pancreatic neuroendocrine neoplasms (pNENs). However, the adverse reactions of Surufatinib should not be ignored in clinical practice. Based on PROTAC technology, we developed a novel tyrosine kinase (TK) degrader PROTAC-Surufatinib (hereinafter referred to as P-Surufatinib). This study was designed to investigate the effects and underlying mechanism of P-Surufatinib on pNENs. In vitro, we revealed that P-Surufatinib could more effectively inhibit proliferation and angiogenesis, and degrade target proteins in pNENs cells than Surufatinib. The transcriptome sequencing revealed that HMOX1 was the key molecule of P-Surufatinib to inhibit proliferation in pNENs. It was demonstrated that HMOX1 was lowly expressed in pNEN

SUBMITTER: Xue B 

PROVIDER: S-EPMC12035883 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature