| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
| Targets |
DZNep targets EZH2 (enhancer of zeste homolog 2), a histone methyltransferase that catalyzes trimethylation of histone H3 at lysine 27 (H3K27me3), and AHCY (S-adenosylhomocysteine hydrolase). By inhibiting EZH2, DZNep reduces H3K27me3 levels and reactivates developmentally silenced genes. Inhibition of AHCY leads to accumulation of S-adenosylhomocysteine, which in turn inhibits methyltransferases, contributing to global histone methylation reduction. This dual mechanism results in epigenetic reprogramming and altered gene expression.
|
|---|---|
| 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].
In vitro, DZNep has been shown to reduce EZH2 expression, with 48%, 32%, and 36% reduction in PANC-1, MIA-PaCa-2, and LPc006 cells, respectively, after 72 hours. Treatment of OCI-AML3 cells with DZNep at 1.0 μM results in significant G0/G1 phase accumulation (58.5%) with decreased S phase (35.2%) and G2/M phase cells (6.3%). The compound inhibits colony growth of OCI-AML3 and HL-60 cells at concentrations of 200 nM to 2.0 μM. In NSCLC cell lines, IC50 values range from 0.08 to 0.24 μM. |
| 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].
In vivo, DZNep has demonstrated anticancer efficacy in preclinical models. In NOD/SCID mice with AML (HL-60 cells), treatment with DZNep and panobinostat significantly improved survival compared to single agents or vehicle alone (median survival: control 36 days; panobinostat 42 days; DZNep 43 days; combination 52 days). In rats, administration of 20 mg/kg DZNep markedly reduced relative body weight compared to initial weight in the first three days post-treatment. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for DZNep measures EZH2 histone methyltransferase activity using purified EZH2 complex and histone substrates. The reaction is performed in optimized buffer containing S-adenosylmethionine (SAM) as methyl donor, and H3K27me3 levels are quantified by ELISA, Western blot, or mass spectrometry. AHCY inhibition is measured by monitoring the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine using coupled enzyme assays or HPLC. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
In vitro cellular studies are conducted using various cancer cell lines including hematologic malignancies (OCI-AML3, HL-60) and solid tumors (PANC-1, MIA-PaCa-2, LPc006, NSCLC cell lines). Cells are treated with DZNep at various concentrations (typically nM to μM) for 48-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Cell cycle analysis is performed by flow cytometry. H3K27me3 and EZH2 levels are measured by Western blot. Colony formation assays evaluate long-term proliferative capacity.
|
| 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 In vivo animal experiments are performed using xenograft models in immunodeficient mice. Tumor-bearing mice are administered DZNep via intraperitoneal injection at doses of 1-20 mg/kg. Tumor volume is measured over time, and endpoints include tumor growth inhibition and survival. Pharmacodynamic studies evaluate H3K27me3 levels, EZH2 expression, and apoptosis markers in tumor tissues. Combination studies with other agents such as panobinostat are performed to evaluate potential synergistic effects. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of DZNep include solubility in water (100 mg/mL with ultrasonication). The compound has a molecular weight of 262.26 g/mol, LogP of 1.48, and appears as a white to off-white solid powder. Boiling point is 541.7±60.0°C at 760 mmHg. Storage at -20°C for powder and -80°C for solutions is recommended. The compound should be protected from light and moisture.
|
| Toxicity/Toxicokinetics |
Toxicological data for DZNep are derived from preclinical studies. The compound has shown weight loss in rats at 20 mg/kg. As an epigenetic modifier, it may have off-target effects and potential toxicity. The compound is for research use only and not intended for human therapeutic applications. Standard safety precautions should be followed when handling the compound due to its potent biological activity.
|
| References |
|
| Additional Infomation |
3-Denitroisoprenic acid A is an imidazopyridine compound.
DZNep is also known as 3-Deazaneplanocin A, NSC 617989, and is supplied as a powder with ≥98% purity. It is a potent histone methyltransferase EZH2 inhibitor and AHCY inhibitor. DZNep has shown anticancer activity in preclinical models of hematologic malignancies and solid tumors. It decreases global histone methylation and reactivates developmentally silenced genes. Ongoing research is exploring combination strategies for enhanced therapeutic efficacy. |
| Molecular Formula |
C12H14N4O3
|
|---|---|
| Molecular Weight |
262.26456
|
| Exact Mass |
262.106
|
| CAS # |
102052-95-9
|
| Related CAS # |
3-Deazaneplanocin A hydrochloride;120964-45-6
|
| PubChem CID |
73087
|
| Appearance |
White to off-white solid powder
|
| Density |
1.6±0.1 g/cm3
|
| Boiling Point |
541.7±60.0 °C at 760 mmHg
|
| Flash Point |
281.4±32.9 °C
|
| Vapour Pressure |
0.0±1.5 mmHg at 25°C
|
| Index of Refraction |
1.753
|
| LogP |
1.48
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
19
|
| 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
|
| InChi Key |
OMKHWTRUYNAGFG-IEBDPFPHSA-N
|
| InChi Code |
InChI=1S/C12H14N4O3/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)/t8-,10-,11+/m1/s1
|
| Chemical Name |
(1S,2R,5R)-5-(4-aminoimidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~381.3 mM; with ultrasonication)
H2O: ~100 mg/mL (~381.3 mM; with ultrasonication) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (9.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
