3-Deazaneplanocin A (DZNep) hydrochloride is a selective inhibitor of ENZ2 inhibitor with IC50 value of 0.08-0.24 μM [1].
ENZ2 is a sub-unit of PRC2 and plays an important role in regulating cell proliferation and cell-cycle progression. It has been reported that ENZ2 is over-expressed in many tumors, including prostate, breast, bladder cancers and AML [2]. In HepG2 cell lines, DZNep treatment markedly induced the intracellular lipids increasement and TNF-αand TGF-βexpression in mRNA level by augmenting PA/OA-dependent lipid accumulation [3].
DZNep is a potent ENZ2 inhibitor. When tested with human acute myeloid leukemia (AML) HL-60 and OCI-AML3 cell lines, administration of DZNep induced cell apoptosis by depleting ENZ2, cyclin E and HOXA9 expressions and inducing p16, p21,p27 and FBXO32 expressions in a dose-dependent manner [2].
In high-fat/high-fructose diet fed (HFa/HFr-D) rat mouse model that resembles human NAFLD metabolically and histologically, DZNep functioned as the effective agent to anti-inflammatory and anti-fibrotic roles by inhibiting ENZ2 [3].
It is also reported that DZNep has the inhibitory activity for (SAHH (S-adenosylhomocysteine hydrolase) with Ki value of 50 pM [4].
References:
[1].?? ?Kikuchi, J., et al., Epigenetic therapy with 3-deazaneplanocin A, an inhibitor of the histone methyltransferase EZH2, inhibits growth of non-small cell lung cancer cells. Lung Cancer, 2012. 78(2): p. 138-43.
[2].?? ?Fiskus, W., 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, 2009. 114(13): p. 2733-43.
[3].?? ?Vella, S., et al., EZH2 down-regulation exacerbates lipid accumulation and inflammation in in vitro and in vivo NAFLD. Int J Mol Sci, 2013. 14(12): p. 24154-68.
[4].?? ?Glazer, R.I., et al., 3-Deazaneplanocin A: a new inhibitor of S-adenosylhomocysteine synthesis and its effects in human colon carcinoma cells. Biochem Pharmacol, 1986. 35(24): p. 4523-7.