3-Deazaneplanocin A

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种高效且具有竞争性的 S-腺苷高半胱氨酸水解酶抑制剂，Ki 为 0.05 nM。

A highly potent and competitive S-adenosylhomocysteine hydrolase inhibitor with Ki of 0.05 nM, also inhibits histone methyltransferase EZH2; more potent than 3-deazaaristeromycin; induces EZH2 protein depletion, leads to cell death in several cancers and tumors; anticancer or antiviral agent.

3-Deazaneplanocin A 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. 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). 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. 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.

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 and Panobinostat (PS) compare to treatment with PS, 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 3-Deazaneplanocin A plus PS, 52 days. 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 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.

NSC 617989 | 3-Deazaneplanocin | DZNep

Chromatin/Epigenetic

HMTase

HMTase

Cancer

——

102052-95-9

262.2646

C12H14N4O3

>98% (HPLC)

10 mM in DMSO

O[C@@H]1[C@H](O)C(CO)=C[C@H]1N2C=NC3=C2C=CN=C3N

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

(-20℃)

With Ice Pack

≥ 2 years