Aphidicolin

Aphidicolin is an inhibitor of DNA polymerase α and δ, prevents mitotic cell division by interfering DNA polymerase activity. Aphidicolin is an antibiotic produced by mold Cephalosporium aphidicola, inhibits cellular deoxyribonucleic acid synthesis and the growth of herpes simplex virus. Aphidicolin exhibits anti-orthopoxvirus activity and potentiates apoptosis induced by arabinosyl nucleosides in a human promyelocytic leukemia cell line^[1][2][3]. In Vitro:Aphidicolin (0.5 μM, 5 μM; 0-5 d) selectively kills neuroblastoma cells, but shows moderate cytotoxicity on normal human embryonal cells and HeLa, H9, A549 and Caco-2 cell lines^[4].
Aphidicolin (0.4 μg/mL; 3 d) arrests cell cycle at G2 phase^[5].
Aphidicolin (100 nM-10 μM; 48 h) inhibits cell proliferation via the p53-GADD45β pathway and (1 μM; 24 h) induces apoptosis in AtT-20 cells^[6].
Aphidicolin (10 μM; 0-6 h) decreases the phosphorylation of Akt, (100 nM-10 μM; 24 h) increases the mRNA levels of the stress response gene growth arrest and DNA damage-inducible 45β (GADD45β), a putative downstream target of p53^[6].
Aphidicolin (10 μM; 0-6 h) inhibits Varicella-zoster virus (VZV) with EC₅₀s of 0.5-0.6 μM, with low cytotoxicity^[7].
In Vivo:Aphidicolin, has been developed with higher solubility agent, namely Aphidicolin glycinate (AG; NSC 303812).
Aphidicolin glycinate (100 mg/kg; i.p.; once every 3 h; 9 d) shows anti-tumor activity against the implanted B16 melanoma and M5076 sarcoma in murine, producing maximum increased life spans of 75%^[8].