A8182-5mg | 3-Deazaneplanocin A (DZNep) hydrochloride [120964-45-6

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.

1. Lin Xu , Jiandong Gao, et al. "Emodin ameliorates tubulointerstitial fibrosis in obstructed kidneys by inhibiting EZH2." Biochem Biophys Res Commun. 2020 Dec 4;S0006-291X(20)32138-0. PMID:33288199
2. Hu W, Jia X, et al. "Chaetospirolactone reverses the apoptotic resistance towards TRAIL in pancreatic cancer." Biochem Biophys Res Commun. 2017 Oct 28. pii: S0006-291X(17)32129-0. PMID:29107694

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	298.73
Cas No.	120964-45-6
Formula	C₁₂H₁₄N₄O₃·HCl
Synonyms	NSC 617989 hydrochloride,DZNep,3-Deazaneplanocin A
Solubility	insoluble in EtOH; ≥14.94 mg/mL in DMSO; ≥18.32 mg/mL in H2O with ultrasonic
Chemical Name	(1S,2R,5R)-5-(4-aminoimidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol;hydrochloride
SDF	Download SDF
Canonical SMILES	C1=CN=C(C2=C1N(C=N2)C3C=C(C(C3O)O)CO)N.Cl
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Cell experiment:[1]
Cell lines	Human acute myeloid leukemia (AML) cell
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	100-750 nM; 24-72h
Applications	DZNep induced apoptosis in cultured and primary AML cells. DZNep exhausted EZH2 levels, and inhibits trimethylation of lysine 27 on histone H3 in the AML HL-60 and OCI-AML3 cells. DZNep induced the levels of p16, p21, p27, and FBXO32 after cyclin E and HOXA9 levels run out.
Animal experiment:[2]
Animal models	Sprague-Dawley rats (120–140 g)
Dosage form	5μM DZNep for 24 h pre-treatment before experiment, orally taken with diets
Applications	DZNep significantly reduced EZH2 expression and activity, and it increased lipid accumulation, inflammatory molecules and microRNAs in non-alcoholic fatty liver disease (NAFLD) mouse model.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: 1. Fiskus W1, 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. 2009 Sep 24;114(13):2733-43. 2. Vella S, Gnani D, Crudele A et al. EZH2 down-regulation exacerbates lipid accumulation and inflammation in vitro and in vivo NAFLD.Int J Mol Sci. 2013 Dec 12;14(12):24154-68.