3-Deazaneplanocin A (hydrochloride)

3-Deazaneplanocin A hydrochloride (DZNep hydrochloride) is a potent histone methyltransferase EZH2 inhibitor^[1][2]. 3-Deazaneplanocin A hydrochlorideis a potent S-adenosylhomocysteine hydrolase (AHCY) inhibitor^[6]. 3-Deazaneplanocin A hydrochloride also has anti-orthopoxvirus and anti-variola activities^[7]. In Vitro:3-Deazaneplanocin A (DZNep) hydrochloride is a potent histone methyltransferase EZH2 inhibitor. Treatment of OCI-AML3 cells with 3-Deazaneplanocin A (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 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].
3-Deazaneplanocin A (DZNep) hydrochloride 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].
3-Deazaneplanocin A (DZNep) hydrochloride 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±0.3 and 0.10±0.03 μM, respectively^[2]. 3-Deazaneplanocin A (DZNep) hydrochloride 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 3-Deazaneplanocin A (DZNep) and LBH589 (PS) compare to treatment with PS, 3-Deazaneplanocin A^[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 3-Deazaneplanocin A (DZNep) 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].