3-deazaneplanocin A HCl (known also as DZNep; C-c3Ado; NSC-617989), the hydrochloride salt of 3-deazaneplanocin A which is an adenosine analog, is a novel and competitive inhibitor of S-adenosylhomocysteine hydrolase and also an EZH2 (histone methyltransferase) inhibitor with anticancer activity. It inhibits S-adenosylhomocysteine hydrolase with a Ki of 50 pM in a cell-free assay. 3-deazaneplanocin A demostrates excellent antiproliferative activity and high in vivo antitumor efficacy. It disrupts polycomb-repressive complex 2 (PRC2), and induces apoptosis, while inhibiting proliferation and metastasis, in cancer cells, including acute myeloid leukemia, breast cancer and glioblastoma. DZNep is a promising therapeutic agent for ovarian cancer cells, with potential to inhibit proliferation, induce apoptosis and decrease migration.

Physicochemical Properties

Molecular Formula	C12H14N4O3.HCL
Molecular Weight	298.73
Exact Mass	298.083
CAS #	120964-45-6
Related CAS #	3-Deazaneplanocin A;102052-95-9;3-Deazaneplanocin A hydrochloride;120964-45-6
PubChem CID	14563109
Appearance	White to light brown solid powder
Melting Point	168-169℃
LogP	0.591
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	2
Heavy Atom Count	20
Complexity	378
Defined Atom Stereocenter Count	3
SMILES	C1=CN=C(C2=C1N(C=N2)[C@@H]3C=C([C@H]([C@H]3O)O)CO)N.Cl
InChi Key	UNSKMHKAFPRFTI-FDKLLANESA-N
InChi Code	InChI=1S/C12H14N4O3.ClH/c13-12-9-7(1-2-14-12)16(5-15-9)8-3-6(4-17)10(18)11(8)19;/h1-3,5,8,10-11,17-19H,4H2,(H2,13,14);1H/t8-,10-,11+;/m1./s1
Chemical Name	(1S,2R,5R)-5-(4-amino-1H-imidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol hydrochloride
Synonyms	NSC 617989 HCl; NSC-617989 HCl; 3-deazaneplanocin A HCl; 3-deazaneplanocin A hydrochloride; DZNep; NSC617989;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	3-Deazaneplanocin A hydrochloride (DZNep) hydrochloride is a potent inhibitor of histone methyltransferase EZH2. Treatment of OCI-AML3 cells with 3-Deazaneplanocin A hydrochloride (1.0 μM) resulted in a significant increase in the accumulation of cells in the G0/G1 phase (58.5%) and concomitant cell numbers in the S phase (35.2%) and G2/M phase (6.3%) of the cell cycle. decreased (P<0.05). Treatment with 3-Deazaneplanocin A hydrochloride (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 hydrochloride (DZNep) hydrochloride can reduce the expression of EZH2, especially after 72 hours (for example, EZH2 in PANC-1, MIA-PaCa-2, and LPc006 cells decreased by 48%, 32%, and 36%, respectively )[2]. 3-Deazaneplanocin A hydrochloride (DZNep) hydrochloride exhibits minimal growth inhibition in PANC-1 cells. When exposed to the greatest dose (20 μM), almost 50% of these cells kept growing. The IC0 values of MIA-PaCa-2 and LPc006 cells are 1.0±0.3 and 0.10±0.03 μM, respectively, indicating their higher sensitivity [2]. 3-Deazaneplanocin A hydrochloride (DZNep) hydrochloride, with IC0 values ranging from 0.08 to 0.24 μM, inhibits NSCLC cell line growth in a dose-dependent manner [3].
ln Vivo	3-Deazaneplanocin A hydrochloride Rats have significantly higher survival rates [1]. Patients with acute myeloid leukemia (AML) caused by HL-60 cells had lower NOD/SCID if treated with 3-Deazaneplanocin A hydrochloride (DZNep) and LBH589 (PS) compared to those treated with PS. In rats given saline, body weight increased gradually over time at an average growth rate of 3.19% per day. When rats were given 20 mg/kg of 3-Deazaneplanocin A hydrochloride (DZNep), their relative body weight decreased significantly in the first three days of treatment (-2.0%, -4.9%, and -1.2%). It also significantly decreased starting on the fourth day of administration. At that point, the daily weight growth rate was suppressed to 2.6% [4].
Animal Protocol	Mice: HL-60 cells (5 million) are injected into the tail vein of female nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and the mice are monitored for 7 days. The following treatments are administered in cohorts of 7 mice for each treatment: vehicle alone, 1 mg/kg 3-Deazaneplanocin A, 10 mg/kg PS, and 3-Deazaneplanocin A plus PS. Treatments are initiated on day 7. 3-Deazaneplanocin A is administered twice per week (Tuesday-Thursday) intraperitoneally for 2 weeks, and then discontinued. PS is administered 3 days per week (Monday, Wednesday, and Friday) for 4 weeks. The survival of mice from the tail vein model is represented with a Kaplan-Meier survival plot. Rats: Male wistar rats are used. The acute toxicity study is carried out to determine the NOAEL of 3-Deazaneplanocin A in rats. In total, 20 rats are divided into 4 groups of five each. Three groups are intravenously administered 20, 15, 10 mg/kg body weight (BW) DZNep solution by the tail vein. The remaining group is given physiological saline (0.9% NaCl saline) as the control group. Then, the NOAEL of free DZNep is determined, depending on the following endpoint parameters obtained. NOD/SCID mice
References	[1]. Fiskus W, et al. Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor LBH589 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 LY 188011 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. [4]. 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. [5]. Noriko Uchiyama, et al. Aristeromycin and DZNeP cause growth inhibition of prostate cancer via induction of mir-26a. Eur J Pharmacol. 2017 Oct 5;812:138-146. [6]. Robert O Baker, et al. Potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections. Antiviral Res. 2003 Jan;57(1-2):13-23

Solubility Data

Solubility (In Vitro)	DMSO: 52 mg/mL (174.1 mM) Water:52 mg/mL (174.1 mM) Ethanol:<1 mg/mL
Solubility (In Vivo)	Solubility in Formulation 1: 50 mg/mL (167.38 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.3475 mL	16.7375 mL	33.4750 mL
	5 mM	0.6695 mL	3.3475 mL	6.6950 mL
	10 mM	0.3348 mL	1.6738 mL	3.3475 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.