Chromomycin A3

Chromomycin A3 is an inhibitor that selectively binds to GC-rich DNA sequences. Chromomycin A3 targets the DNA minor groove after forming a dimer with Mg²⁺. Chromomycin A3 inhibits DNA replication and transcription, blocks the binding of Sp1 transcription factor to target gene promoters, downregulates the expression of anti-apoptotic proteins such as FLIP, Mcl-1, and XIAP, and induces S-phase cycle arrest and caspase-dependent apoptosis in tumor cells. Chromomycin A3 can antagonize oxidative stress induced by glutathione depletion and neuronal apoptosis induced by Camptothecin (HY-15660). Chromomycin A3 can be used in basic research on malignant tumors such as cholangiocarcinoma, and is a potential chemosensitizer and GC-rich region probe^[1][2][3]. In Vitro:Chromomycin A3 (2.5-160 nM; 24 h, 48 h) inhibits the proliferation of cholangiocarcinoma cells KKU-213, KKU-055, and KKU-100 in a dose- and time-dependent manner, with IC₅₀s ??of 22.48 nM, 21.14 nM, and 30.52 nM at 24 h, respectively.
Chromomycin A3 (2.5-10 nM; 24 h) induces S phase arrest of KKU-213 and KKU-055 cells at low concentrations. At high concentrations, Chromomycin A3 (10-40 nM; 24 h) induces dose-dependent apoptosis by activating the caspase-8/-9/-3 pathway, and the proportion of early and late apoptotic cells increased significantly^[1]. In Vivo:Chromomycin A3 (0.5 mg/kg; i.v.; once per week; 3 weeks) significantly inhibits tumor growth in the Rag-2/Jak3 double-deficient mouse cholangiocarcinoma xenograft model without obvious toxicity^[1].