Dehydroaltenusin

Dehydroaltenusin is a small molecule selective inhibitor of eukaryotic DNA polymerase α, a type of antibiotic produced by a fungus with an IC50 value of 0.68 μM. The inhibitory mode of action of dehydroaltenusin against mammalian pol α activity is competitive with respect to the DNA template primer (Ki=0.23 µM) and non-competitive with respect to the 2'-deoxyribonucleoside 5'-triphosphate substrate (Ki=0.18 µM)[1].Dehydroaltenusin arrests the cancer cell cycle at the S-phase and triggers apoptosis[1].Dehydroaltenusin possesses anti-tumor activity against human adenocarcinoma tumor in vivo[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

IC50: 0.68 μM (DNA polymerase α)[1]

Dehydroaltenusin (38.0-44.4 μM; 24 hours) inhibits cell growth in a dose-dependent manner and the LD50 values varies from 38.0 to 44.4 μM[1]. Dehydroaltenusin (38.0 μM; 6 hours) inhibits cell growth by blocking the S-phase of DNA replication[1]. Dehydroaltenusin (75.0 μM; 24 hours) has a strong apoptotic effect on human cancer cells, DNA ladders can be detected after 12 h of incubation with dehydroaltenusin[1]. Cell Proliferation Assay[1] Cell Line: Human cancer cell line: A549, BALL-1, HeLa and NUGC-3 cells Concentration: 38.0-44.4 μM Incubation Time: 24 hours Result: Inhibited cell growth of human cancer cell lines. Cell Cycle Analysis[1] Cell Line: HeLa cells Concentration: 38.0 μM Incubation Time: 6 hours Result: Decreased to 45% of the control value after 6 h of incubation [3H]-thymidine. Apoptosis Analysis[1] Cell Line: HeLa cells Concentration: 75.0 μM Incubation Time: 12-24 hours Result: Detected DNA ladders after 12 hours of incubation.

Dehydroaltenusin (injection; 20 mg/kg; 2-day intervals; 12-39 days) shows suppressed tumor growth from 21 days[1]. Animal Model: Nude mice bearing HeLa solid tumors[1] Dosage: 20 mg/kg Administration: Injection; 20 mg/kg; 2-day intervals; 12-39 days Result: Suppressed tumor growth.

[1]. Mizushina Y, et al. Dehydroaltenusin is a specific inhibitor of mammalian DNA polymerase α. Expert Opin Investig Drugs. 2011 Nov;20(11):1523-34.