Disclosed are blocking peptides and related methods, formulations, and compositions, pertaining to the field of
biomedicine. Based on the regulatory mechanism by which the
negative regulator TGF-β modulates the transport and degradation of STING, the use of AP3D1 as a
drug target for
in vitro screening of blocking agents is provided to identify the S9 regulatory site and the R26 regulatory site of AP3D1. Corresponding blocking peptides targeting the S9 regulatory site and the R26 regulatory site, respectively, were synthesized to specifically inhibit AP3D1-mediated inactivation of STING signaling by
tumor microenvironment factors, thereby blocking at least one of the S9 regulatory site and the R26 regulatory site and effectively restricting STING transport and degradation. The blocking
peptide can synergize with various treatment modalities, including
chemotherapy, radiotherapy, PARP inhibitors, and STING agonists, significantly enhancing cGAS-STING signaling activation in tumors during therapy and achieving more potent antitumor
efficacy.