Sinefungin is a purine nucleoside and derivative of S-adenosylhomocysteine that has been found in Streptomyces and has diverse biological activities.[1],[2] It inhibits G9a methyltransferase and SET domain-containing protein 7 (SET7) with IC50 values of 10.4 and 2.38 µM, respectively, using histone H3 (1-21) peptide as a substrate and 150 and 9.1 µM, respectively, using full-length histone H3 as a substrate.[3] It also inhibits protein arginine methyltransferase 5 (PRMT5) with IC50 values of 0.31 and 0.69 µM using histone H4 (1-21) peptide and full-length histone H4, respectively, as substrates. Sinefungin (10 mg/kg) reduces renal levels of the mesenchymal marker α-smooth muscle actin (α-SMA), fibrosis markers ferroptosis suppressor protein 1 (Fsp1), collagen 1, collagen 3, and fibronectin, and monomethylation of histone H3 lysine 4 (H3K4me1) in a mouse model of unilateral ureteral obstruction.[4]
References:
[1].Nolan, L.L.Molecular target of the antileishmanial action of sinefunginAntimicrob. Agents Chemother.31(10)1542-1548(1987).
[2].Maguire, M.P., Feldman, P.L., and Rapoport, H.Stereoselective synthesis and absolute stereochemistry of sinefunginJ. Org. Chem.55(3)948-955(1990).
[3].Horiuchi, K.Y., Eason, M.M., Ferry, J.J., et al.Assay development for histone methyltransferasesAssay Drug Dev. Technol.11(4)227-236(2013).
[4].Sasaki, K., Doi, S., Nakashima, A., et al.Inhibition of SET domain-containing lysine methyltransferase 7/9 ameliorates renal fibrosisJ. AM. Soc. Nephrol.27(1)203-215(2016).