Discovery of novel benzylquinazoline molecules as p97/VCP inhibitors.

ABSTRACT: Introduction: Protein p97 is an extensively investigated AAA ATPase with various cellular activities, including cell cycle control, ubiquitin-proteasome system, autophagy, and NF-κB activation. Method: In this study, we designed, synthesized and evaluated eight novel DBeQanalogs as potential p97 inhibitors in vivo and in vitro. Results: In the p97 ATPase inhibition assay, compounds 6 and 7 showed higher potency than the known p97 inhibitors, DBeQ and CB-5083. Compounds 4-6 dramatically induced G0/G1 phase arrest in the HCT116 cells, and compound 7 arrested the cells in both G0/G1 and S phases. Western blots showed elevated levels of SQSTM/p62, ATF-4, and NF-κB in HCT116 cells with the treatment of compounds 4-7, confirmi

SUBMITTER: Zhang X 

PROVIDER: S-EPMC10300352 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature