3-Deazaneplanocin A

3-Deazaneplanocin A is a cyclopentenyl analog of 3-deazaadenosine, originally synthesized as an inhibitor of S-adenosyl-L-homocysteine hydrolase.¹ It has been shown to deplete EZH2 levels and to inhibit trimethylation of lysine 27 on histone H3 in cultured human acute myeloid leukemia (AML) HL-60 and OCI-AML3 cells and in primary AML cells in a dose-dependent manner (0.2-1 μM).² 3-Deazaneplanocin A treatment of cultured human AML cells induces increased expression of the cell-cycle regulators p21, p27, and FBXO32, leading to cell cycle arrest and apoptosis.² When used in combination with the pan-histone deacetylase inhibitor panobinostat (10 mg/kg), 3-deazaneplanocin A’s (1 mg/kg) antileukemic effects are synergistically enhanced in mice implanted with AML cells.^2,3

WARNING This product is not for human or veterinary use.

1. Tseng, C.K.H., Marquez, V.E., Fuller, R.W., et al. Synthesis of 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase with potent and selective in vitro and in vivo antiviral activities. J. Med. Chem. 32(7), 1442-1446 (1989).

2. Fiskus, W., Wang, Y., Sreekumar, A., et al. Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood 114(13), 2733-2743 (2009).

3. Bissinger, E.M., Heinke, R., Sippl, W., et al. Targeting epigenetic modifiers: Inhibitors of histone methyltransferases. Med. Chem. Commun. 1(2), (2010).