ACJI-99C

ACJI-99C (VCP/p97-IN-PPA) is a selective covalent p97/VCP ATPase inhibitor with an IC₅₀ value of 0.6 μM. ACJI-99C binds with p97 active site residues to block ATPase activity. ACJI-99C irreversibly blocks degradation of p97-dependent protein in cells. ACJI-99C inhibits proliferation of cancer cells, including p97 inhibitor-resistant lines. ACJI-99C can be used for the research of colorectal cancer^[1]. In Vitro:ACJI-99C (Compound 18) (60 min) potently and selectively inhibits wild-type human p97 ATPase activity via covalent targeting of Cys522, with an IC₅₀ of 0.62 μM, while showing drastically reduced activity against p97 Cys522 mutants, wild-type yeast Cdc48, hamster NSF, and human 19S ATPase^[1].
ACJI-99C (120 min) selectively and irreversibly inhibits p97-dependent protein degradation in HeLa cells, with an IC₅₀ of 1.6 μM for UbG76V-GFP degradation, and 22-fold lower activity against p97-independent ODD-Luc degradation^[1].
ACJI-99C (48 h) inhibits proliferation of HCT116, HeLa, and RPMI8226 cancer cell lines with IC₅₀ values ranging from 2.7 μM to 6.1 μM, and retains comparable activity against CB-5083-resistant and NMS-873 (HY-15713)-resistant HCT116 cell lines^[1].
ACJI-99C (10 μM; 60-120 min) blocks degradation of the ERAD substrate TCRα-GFP in HEK293 cells after 60 and 120 minutes of incubation^[1].
ACJI-99C (15-30 μM; 6 h) alters the abundance of p97-interacting proteins and induces enrichment of p97-related functional pathways in HCT116 cells, with concentration-dependent changes in key proteins like SQSTM1 and GOLGA3^[1].
ACJI-99C (5-50 μM; 30 min) does not inhibit human 26S proteasome activity^[1].