3-Deazaneplanocin,DZNep
3-Deazaneplanocin (DZNep) (CAS No.102052-95-9) is an inhibitor of the enzyme S-adenosylhomocysteine hydrolase (SAHH), exerting its inhibitory activity via competitive interaction with adenosine. Its inhibition constant (Ki) against SAHH is approximately 0.05 nM. Additionally, 3-Deazaneplanocin suppresses the activity of histone methyltransferase EZH2. Studies in human leukemia HL-60 cells reported a moderate reduction of cellular proliferation at concentration of 10 μM. In hepatocellular carcinoma (HCC) cell lines (Huh1 and Huh7), treatment led to a dose-dependent inhibition in cell growth and reduced formation of non-adherent spheres. In vivo, the compound limited tumor initiation and growth in mouse xenograft models, suggesting utility in oncology research for targeting tumor-initiating cell populations.
References:
[1] Glazer R I, Hartman K D, Knode M C, et al. 3-Deazaneplanocin: a new and potent inhibitor of S-adenosylhomocysteine hydrolase and its effects on human promyelocytic leukemia cell line HL-60. Biochemical and biophysical research communications, 1986, 135(2): 688-694.
[2] Chiba T, Suzuki E, Negishi M, et al. 3-Deazaneplanocin A is a promising therapeutic agent for the eradication of tumor-initiating hepatocellular carcinoma cells. International Journal of Cancer, 2012, 130(11): 2557-2567.
- 1. Wenliang Li, Dayong Zheng, et al. "Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB1/EZH2-mediated downregulation of REST." Res Sq. 2023 Oct 4:rs.3.rs-3270539. PMID: 37886478
- 2. Weiyun Wang, Shaofang Ren, et al. "Inhibition of Syk promotes chemical reprogramming of fibroblasts via metabolic rewiring and H2S production." EMBO J. 2021 Jun 1;40(11):e106771. PMID:33909912
- 3. Xu W, Huang M, et al. "The Role of CHK1 Varies with the Status of Oestrogen-receptor and Progesterone-receptor in the Targeted Therapy for Breast Cancer." Int J Biol Sci. 2020;16(8):1388-1402. PMID:32210727
- 4. Bassem Merit,Shoucri. "Retinoid X Receptor Activation by the Endocrine Disruptor Tributyltin Promotes Adipose Lineage Commitment and Perturbs Adipocyte Function" UNIVERSITY OF CALIFORNIA.2018.
- 5. Hardik Rameshchandra Mody. "Investigation of Micro-RNA-based Approaches to Overcome Epithelial-Mesenchymal Transition in Pancreatic Cancer" Ohio State University.2017. PMID:29498802
- 6. Lin B, Coleman JH, et al."Injury Induces Endogenous Reprogramming and Dedifferentiation of Neuronal Progenitors to Multipotency." Cell Stem Cell. 2017 Nov 20. pii: S1934-5909(17)30375-2. PMID:29174332
- 7. Shi X, Tasdogan A, et al. "The abundance of metabolites related to protein methylation correlates with the metastatic capacity of human melanoma xenografts." Sci Adv. 2017 Nov 1;3(11):eaao5268. PMID:29109980
- 8. Bassem M. Shoucri, Eric S. Martinez, et al. "Retinoid X receptor activation alters the chromatin landscape to commit mesenchymal stem cells to the adipose lineage." Endocrinology. 2017 Jul.
- 9. Yang SZ, Xu F, et al. "The long non-coding RNA HOTAIR enhances pancreatic cancer resistance to TNF-related apoptosis-inducing ligand." J Biol Chem. 2017 Jun 23;292(25):10390-10397. PMID:28476883
| Physical Appearance | A crystalline solid |
| Storage | Store at -20°C |
| M.Wt | 262.26 |
| Cas No. | 102052-95-9 |
| Formula | C12H24N4O3 |
| Synonyms | DZNep, 3-Deazaneplanocin A,NSC 617989,NSC617989 |
| Solubility | insoluble in EtOH; ≥17.07 mg/mL in DMSO; ≥17.43 mg/mL in H2O |
| Chemical Name | (1S,2R,5R)-5-(4-aminoimidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol |
| SDF | Download SDF |
| Canonical SMILES | Nc1nccc2c1nc[n]2[C@@H]([C@@H]1O)C=C(CO)[C@H]1O |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
Human acute myeloid leukemia (AML) cell |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
100-750 nM; 24-72h |
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Applications |
DZNep induced apoptosis in cultured and primary AML cells. DZNep exhausted EZH2 levels, and inhibits trimethylation of lysine 27 on histone H3 in the AML HL-60 and OCI-AML3 cells. DZNep induced the levels of p16, p21, p27, and FBXO32 after cyclin E and HOXA9 levels run out. |
| Animal experiment:[2] | |
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Animal models
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Sprague-Dawley rats (120–140 g) |
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Dosage form
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5μM DZNep for 24 h pre-treatment before experiment, orally taken with diets |
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Applications |
DZNep significantly reduced EZH2 expression and activity, and it increased lipid accumulation, inflammatory molecules and microRNAs in non-alcoholic fatty liver disease (NAFLD) mouse model. |
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Fiskus W1, Wang Y, Sreekumar A 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 Sep 24;114(13):2733-43. 2. Vella S, Gnani D, Crudele A et al. EZH2 down-regulation exacerbates lipid accumulation and inflammation in vitro and in vivo NAFLD.Int J Mol Sci. 2013 Dec 12;14(12):24154-68. |
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| Description | 3-deazaneplanocin A (DZNeP), an analog of adenosine, is a competitive inhibitor of S-adenosylhomocysteine hydrolase with Ki of 50 pM. | |||||
| Targets | S-adenosylhomocysteine hydrolase | |||||
| IC50 | 50 pM (Ki) | |||||
Quality Control & MSDS
- View current batch:
-
Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
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