tcsc0357 DZNep

DZNep (3-Deazaneplanocin A) is a potent histone methyltransferase EZH2 inhibitor.

IC50 & Target: EZH2^[1]

In Vitro: DZNep (3-Deazaneplanocin A) is a potent histone methyltransferase EZH2 inhibitor. Treatment of OCI-AML3 cells with DZNep (1.0 μM) results in a significant increase in accumulation of cells in the G₀/G₁ phase (58.5%) with a concomitant decrease in the number of cells in S phase (35.2%) and G₂/M phases (6.3%) of the cell cycle (P<0.05). Treatment with DZNep (3-Deazaneplanocin A) (200 nM to 2.0 μM) for 48 hours, dose dependently, inhibits colony growth of OCI-AML3 and HL-60 cells^[1]. DZNep (3-Deazaneplanocin A) reduces the expression of EZH2, especially after 72 hours (e.g. 48%, 32% and 36% reduction of EZH2 in PANC-1, MIA-PaCa-2 and LPc006 cells, respectively)^[2]. DZNep (3-Deazaneplanocin A) shows minimal growth inhibition in PANC-1 cells. More than 50% of these cells are still growing after exposure at the highest concentration (20 μM). MIA-PaCa-2 and LPc006 cells are much more sensitive, with IC₀ values of 1±0.3 and 0.1±0.03 μM, respectively^[2]. DZNep (3-Deazaneplanocin A) causes dose-dependent inhibition of cell proliferation of NSCLC cell lines, and the IC₀ values range from 0.08 to 0.24 μM^[3].

In Vivo: The survival of NOD/SCID mice with acute myeloid leukemia (AML) due to HL-60 cells is significantly higher, if treated with DZNep and Panobinostat (PS) compare to treatment with PS, DZNep (3-Deazaneplanocin A), or vehicle alone (P<0.05). Median survival is as follows: control, 36 days; PS, 42 days; 3-Deazaneplanocin A, 43 days; and DZNep (3-Deazaneplanocin A) plus PS, 52 days^[1]. There is a progressive increase in weight of rats treated with physiological saline in a time-dependent manner (the mean growth rate=3.19% per day). Administration of 20 mg/kg DZNep (3-Deazaneplanocin A) not only markedly reduces the relative weight of the rats compare to the initial weight (−2.0%, −4.9% and −1.2%) in the first three days post-treatment, but also suppresses the weight growth rate to 2.6% per day from the fourth day onwards post-dose^[4].