3-Deazaneplanocin A hydrochloride [EZH2 Inhibitor]

Histone methyltransferase inhibitor. Inhibit the expression of S-adenosyl homocysteine hydrolase (SAH) and EZH2 protein. It also enhance Oct4 expression in chemically induced pluripotent stem cells. Exhibits anti-cancer and anti-viral effects.

DZNep hydrochloride; NSC 617989 hydrochloride; 3-Deazaneplanocin hydrochloride

(1S,2R,5R)-5-(4-Amino-1H-imidazo[4, 5-c]pyridin-1-yl)-3-(hydroxymethyl)-3-cyclopentene -1,2-diol hydrochloride

Inhibitor

Neurological Disorders

3-Deazaneplanocin A (DZNep) hydrochloride is a potent histone methyltransferase EZH2 inhibitor. Treatment of OCI-AML3 cells with 3-Deazaneplanocin A (1.0 μM) resulted in a significant increase in cell accumulation in the G0/G1 phase (58.5%), as well as a reduction in the number of cells in the S phase (35.2%) and G2/M phase (6.3%)) Of the cell cycle (P<0.05). 3-Deazaneplanocin A (200 nM to 2.0 μM) treatment for 48 hours dose-dependently inhibited the colony growth of OCI-AML3 and HL-60 cells [1]. 3-Deazaneplanocin A (DZNep) hydrochloride can reduce the expression of EZH2, especially after 72 hours (for example, the reduction of EZH2 in PANC-1, MIA-PaCa-2 and LPc006 cells is 48%, 32% and 36%, respectively))[2]. 3-Deazaneplanocin A (DZNep) hydrochloride showed minimal growth inhibition in PANC-1 cells. After exposure to the highest concentration (20 μM), more than 50% of these cells were still growing. MIA-PaCa-2 and LPc006 cells are more sensitive, with IC0 values ​​of 1.0±0.3 and 0.10±0.03μM, respectively [2]. 3-Deazaneplanocin A (DZNep) hydrochloride has a dose-dependent inhibitory effect on cell proliferation of NSCLC cell lines, with IC0 values ​​ranging from 0.08 to 0.24 μM [3].

[1]. 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), 2733-2743.

[2]. Avan A, et al. Molecular mechanisms involved in the synergistic interaction of the EZH2 inhibitor 3-deazaneplanocin A with gemcitabine in pancreatic cancer cells. Mol Cancer Ther. 2012 Aug;11(8):1735-46.

[3]. 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 Nov;78(2):138-43.

If treated with 3-Deazaneplanocin A (DZNep) and Panobinostat (PS), compared with PS, 3-Deazaneplanocin A, the survival rate of NOD/SCID mice due to HL-60 cells is higher due to HL-60 cells Much more. Or use the medium alone (P <0.05). The median survival time is as follows: control group, 36 days; PS, 42 days; 3-Deazaneplanocin A, 43 days; and 3-Deazaneplanocin A plus PS, 52 days [1]. The body weight of rats treated with physiological saline gradually increased in a time-dependent manner (average growth rate = 3.19%/day). Compared with the initial body weight (-2.0%, -4.9% and -1.2%) in the first three days after treatment, administration of 20 mg/kg 3-Deazaneplanocin A (DZNep) not only significantly reduced the relative weight of From the fourth day after medication, the growth rate of body weight can still be suppressed to 2.6% per day [2].

[1]. 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), 2733-2743.

[2]. Sun F, et al. Preclinical pharmacokinetic studies of 3-deazaneplanocin A, a potent epigenetic anticancer agent, and its human pharmacokinetic prediction using GastroPlus?. Eur J Pharm Sci. 2015 Sep 18;77:290-302.

298.73

Powder

C12H14N4O3.HCl

Synthetic

OCC([C@@H](O)[C@H]3O)=C[C@H]3N2C=NC1=C(N)N=CC=C12.Cl

Soluble in water (10mM)

120964-45-6

14563109

>98%

-20°C

Room Temperature

For obtaining a higher solubility, please warm the tube at 37 °C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -34°C for several months.

For research use only

EZH2

EZH2

Enhancer of zeste homolog 2

EZH2, ENX-1, ENX1, EZH1, EZH2b, KMT6, KMT6A, WVS, WVS2, enhancer of zeste 2 polycomb repressive complex 2 subunit

2146(Human); 14056(Mouse); 312299(Rat)