Pyrazofurin

Pyrazofurin is a nucleoside derivative that has been found in S. candidus and has antiviral and anticancer activities.^1,2,3 It is an inhibitor of orotidine-5’-monophosphate decarboxylase (OMP decarboxylase) that inhibits DNA synthesis.² Pyrazofurin inhibits the cytopathic effect of parainfluenza-3 virus, measles virus, vaccinia virus, and herpes simplex virus 2 (HSV-2) in Vero cells (EC₅₀s = 3, 9.6, 2.8, and 20 µM, respectively).¹ It also reduces infection of Calu-3 cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a synergistic effect when used in combination with molnupiravir (Item No. 29586) or remdesivir (Item No. 30354).³ Pyrazofurin reduces tumor growth in L1210 and P388 leukemia, Lewis lung, and B16 murine melanoma models (ID₅₀s = 3.2, 3.3, 1.8, and 63 nM, respectively).¹

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1. Petrie, C.R., 3rd., Revankar, G.R., Dalley, N.K., et al. Synthesis and biological activity of certain nucleoside and nucleotide derivatives of pyrazofurin. J. Med. Chem. 29(2), 268-278 (1986).

2. Ringer, D.P., Howell, B.A., and Etheredge, J.L. Alteration in de novo pyrimidine biosynthesis during uridine reversal of pyrazofurin-inhibited DNA synthesis. J. Biochem. Toxicol. 69(1), 19-27 (1991).

3. Schultz, D.C., Johnson, R.M., Ayyanathan, K., et al. Pyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2. Nature 604(7904), 134-140 (2022).