CBP-93872

CBP-93872 is a G2 checkpoint inhibitor and a chemosensitizer. CBP-93872 specifically inhibits DNA double-strand break (DSB)-dependent, Nbs1-mediated ATR activation, without directly inhibiting ATR kinase activity or affecting ATR activation induced by other types of DNA damage; meanwhile, it suppresses the pathway between ATM and ATR activation, thereby reducing the autophosphorylation of ATR and the subsequent phosphorylation of Chk1. CBP-93872 does not inhibit DNA end resection at DSB sites. CBP-93872 induces cell death and enhances the cytotoxic effects of platinum-containing compounds and pyrimidine antimetabolites on cancer cells. CBP-93872 can be used in related research on p53-mutant cancers, colorectal cancer, and pancreatic cancer^[1][2]. In Vitro:CBP-93872 (20 μM) abrogates the maintenance of IR-induced G₂ checkpoint in p53-deficient HT-29, A549 and NCI-H460 cells, but does not affect its initiation; whereas in MCF7 cells with normal p53 function, this compound does not alter the IR-induced G₂ checkpoint ^[1].
CBP-93872 (20 μM) specifically inhibits DSB-induced ATR activation and the downstream ATR-dependent phosphorylation of Chk1, Nbs1, and RPA2 in HT-29 cells, without affecting ATM activation and non-DSB-induced checkpoint signaling pathways^[1].
CBP-93872 (>50 μM; 72 h) inhibits the proliferation of colorectal cancer HT29 cells at concentrations above 50 μM after 72 h of treatment^[2].
CBP-93872 (>200 μM; 72 h) inhibits the proliferation of Panc-1 pancreatic cancer cells at a concentration higher than 200 μM after 72 h of treatment^[2].
CBP-93872 (50 μM; 72 h) enhances Oxaliplatin-induced apoptosis in colorectal cancer HT29 cells, increases the proportion of sub-G1 phase cells to 24.3% after 72 h of combined treatment, and upregulates the expression levels of cleaved caspase 3 and γH2AX^[2].
CBP-93872 (50 μM; 48 h) abolishes Oxaliplatin (HY-17371)-induced G2 checkpoint activation in HT29 colorectal cancer cells^[2].
CBP-93872 (50 μM; 48 h) abrogates the G2 checkpoint activation induced by Cisplatin (HY-17394) in HT29 colorectal cancer cells^[2].