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3-Deazaneplanocin A (C-c3Ado, DZNep; NSC617989) is an adenosine analogue acting as a competitive inhibitor of S-adenosylhomocysteine hydrolase and EZH2 (histone methyltransferase). It exhibits anticancer activity by inhibiting 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. In addition, 3-Deazaneplanocin A was also found to be effective for the treatment of Ebola virus disease, apparently interfering with the Ebola viruses ability to block interferon production, thus restoring the ability of immune system to rid the body of ebolavirus.
| ln Vitro |
3-Deazaneplanocin A is an effective inhibitor of histone methyltransferase EZH2. Treatment of OCI-AML3 cells with 3-Deazaneplanocin A (1.0 μM) causes a significant drop in the number of cells in the S phase (35.2%) and G2/M phases (6.3%) of the cell cycle (P<0.05), along with an increase in the accumulation of cells in the G0/G1 phase (58.5%). OCI-AML3 and HL-60 cell colony growth is inhibited when treated with 3-Deazaneplanocin A (200 nM to 2.0 μM) for 48 hours, in a dose-dependent manner[1]. 3-Deazaneplanocin A inhibits EZH2 expression, particularly after 72 hours (EZH2 expression in PANC-1, MIA-PaCa-2, and LPc006 cells, respectively, is reduced by 48%, 32%, and 36%)[2]. 3. In PANC-1 cells, dexapeneplanocin A exhibits negligible growth inhibition. Once exposed to the greatest dose (20 μM), almost 50% of these cells continue to develop. The IC0 values of MIA-PaCa-2 and LPc006 cells are significantly higher, at 1±0.3 and 0.1±0.03 μM, respectively[2]. 3-Deazaneplanocin A has an IC0 range of 0.08 to 0.24 μM and inhibits NSCLC cell line proliferation in a dose-dependent manner[3].
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| ln Vivo |
When 3-Deazaneplanocin A and Panobinostat (PS) are administered together, NOD/SCID mice with acute myeloid leukemia (AML) caused by HL-60 cells have a considerably greater survival rate (P<0.05) than when PS, 3-Deazaneplanocin A, or vehicle alone are treated. The following are the median survival times: 36 days for control, 42 days for PS, 43 days for 3-Deazaneplanocin A, and 52 days for 3-Deazaneplanocin A plus PS[1]. Rats given physiological saline saw a time-dependent, gradual gain in weight (mean growth rate = 3.19%/day). When 20 mg/kg 3-Deazaneplanocin A is administered to rats, it not only significantly lowers their relative weight in comparison to their starting weight (−2.0%, −4.9%, and −1.2%) in the first three days after treatment, but it also slows their weight growth rate, which drops to 2.6% per day on the fourth day after the dose[4].
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| Animal Protocol |
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| References |
[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. [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]. Siddiqi FS, et al. The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in Diabetes. J Am Soc Nephrol. 2016 Jul;27(7):2021-34. [6]. 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. [7]. Smee DF, et al. A review of compounds exhibiting anti-orthopoxvirus activity in animal models. Antiviral Res. 2003 Jan;57(1-2):41-52 |
| Molecular Formula |
C12H14N4O3
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|---|---|
| Molecular Weight |
262.26456
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| CAS # |
102052-95-9
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| Related CAS # |
3-Deazaneplanocin A hydrochloride;120964-45-6
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| SMILES |
O[C@@H]1[C@H](O)C(CO)=C[C@H]1N2C=NC3=C2C=CN=C3N
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8130 mL | 19.0650 mL | 38.1301 mL | |
| 5 mM | 0.7626 mL | 3.8130 mL | 7.6260 mL | |
| 10 mM | 0.3813 mL | 1.9065 mL | 3.8130 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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