3-Deazaneplanocin A (DZNep) hydrochloride (Synonyms: 2,3DMMC) |
| رقم الكتالوجGC17907 |
مثبط لإنزيم الميثيل ترانسفيراز EZH2 الذي يعمل على إضافة مجموعات الميثيل على الأحماض الأمينية من نوع اللايسين.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 120964-45-6
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
3-Deazaneplanocin A (DZNep) hydrochloride is an adenosine analogue and is a competitive S-adenosylhomocysteine hydrolase inhibitor with a Ki of 50 pM in cell-free tests.This results in the intracellular accumulation of AdoHcy, which leads to inhibition of the S-adenosyl-l-methionine dependent KMTase activity[1-2,5].3-Deazaneplanocin A (DZNep) hydrochloride has also been shown to inhibit the activity of the methyltransferases, resulting in undermethylation of mRNAs[3].
3-Deazaneplanocin A (DZNep) hydrochloride (100-750 nmol/L; 48 hours) treatment induces cell-cycle arrest and apoptosis, and markedly reduces clonogenic survival of AML cells[4]. 3-Deazaneplanocin A (DZNep) hydrochloride was reported to deplete the expression levels of the PRC2 complex in breast cancer cells with concomitant loss of 3Me H3K27 mark and derepression of epigenetically silenced targets[6]. 3-Deazaneplanocin A (DZNep) hydrochloride(10-6M-10-5M ;2 days)displayed excellent antiviral activity in cell culture against vesicular stomatitis, parainfluenza type 3, yellow fever, and vaccinia viruses[1].
3-Deazaneplanocin A (DZNep) hydrochloride (1 mg/kg; i.p.; 2 weeks) and panobinostat induced apoptosis of AML cells and significantly improved the survival rate of non-obese diabetic/severely immunodeficient mice with HL-60 leukemia [4]. 3-Deazaneplanocin A (DZNep)(i.p.; 0.5-1.5 mg/kg/d; 2 weeks)can significantly reduce the incidence of leishmania infection in skin of inbred BALB/c mice induced by L. b. guyanensis inoculation [7].
References:
[1]. Glazer RI, Hartman KD, et,al.3-Deazaneplanocin: a new and potent inhibitor of S-adenosylhomocysteine hydrolase and its effects on human promyelocytic leukemia cell line HL-60. Biochem Biophys Res Commun. 1986 Mar 13;135(2):688-94. doi: 10.1016/0006-291x(86)90048-3. PMID: 3457563.
[2]. Bray M, Driscoll J, et,al.Treatment of lethal Ebola virus infection in mice with a single dose of an S-adenosyl-L-homocysteine hydrolase inhibitor. Antiviral Res. 2000 Feb;45(2):135-47. doi: 10.1016/s0166-3542(00)00066-8. PMID: 10809022.
[3]. Jiang X, Tan J, et,al. DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications. Cancer Cell. 2008 Jun;13(6):529-41. doi: 10.1016/j.ccr.2008.04.019. PMID: 18538736; PMCID: PMC2577847.
[4]. Fiskus W, Wang Y, 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. doi: 10.1182/blood-2009-03-213496. Epub 2009 Jul 28. PMID: 19638619; PMCID: PMC2756128.
[5]. Tseng CK, Marquez VE, Fuller RW, Goldstein BM, Haines DR, McPherson H, Parsons JL, Shannon WM, Arnett G, Hollingshead M, et al. Synthesis of 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase with potent and selective in vitro and in vivo antiviral activities. J Med Chem. 1989 Jul;32(7):1442-6. doi: 10.1021/jm00127a007. PMID: 2544721.
[6]. Tan J, Yang X, et,al. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev. 2007 May 1;21(9):1050-63. doi: 10.1101/gad.1524107. Epub 2007 Apr 16. PMID: 17437993; PMCID: PMC1855231.
[7]. Avila JL, Avila A, et,al.Specific inhibitory effect of 3-deazaneplanocin A against several Leishmania mexicana and L. braziliensis strains. Am J Trop Med Hyg. 1997 Oct;57(4):407-12. doi: 10.4269/ajtmh.1997.57.407. PMID: 9347954.
| Cell experiment [1]: | |
|
Cell lines |
OCI-AML3 cells |
|
Preparation Method |
Cells were treated with a specified concentration of DZNep for 24 h. |
|
Reaction Conditions |
DZNep (0/1.0 µM); 24 h |
|
Applications |
Treatment of OCI-AML3 cells with DZNep (1.0 µM) resulted in a significant increase in accumulation of cells in the G0/G1 phase with a concomitant decrease in the number of cells in S phase and G2/M phases of the cell cycle. |
| Animal experiment [2]: | |
|
Animal models |
Female nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice |
|
Preparation Method |
HL-60 cells (5 million) were injected into the tail vein of mice. The following treatments were administered in cohorts of 7 mice for each treatment: vehicle alone, 1 mg/kg DZNep, 10 mg/kg PS, and DZNep plus PS. Treatments were initiated on day 7. DZNep was administered twice per week intraperitoneally for 2 weeks, and then discontinued. |
|
Dosage form |
1 mg/kg DZNep; i.p.; twice a week for 2 weeks |
|
Applications |
NOD/SCID mice treated with DZNep had significantly improved survival from AML caused by HL-60 cells. |
|
References: [1]. Tseng CK, Marquez VE, Fuller RW, Goldstein BM, Haines DR, McPherson H, Parsons JL, Shannon WM, Arnett G, Hollingshead M, et al. Synthesis of 3-deazaneplanocin A, a powerful inhibitor of S-adenosylhomocysteine hydrolase with potent and selective in vitro and in vivo antiviral activities. J Med Chem. 1989 Jul;32(7):1442-6. doi: 10.1021/jm00127a007. PMID: 2544721. | |
| Cas No. | 120964-45-6 | SDF | |
| المرادفات | 2,3DMMC | ||
| Chemical Name | (1S,2R,5R)-5-(4-aminoimidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol;hydrochloride | ||
| Canonical SMILES | C1=CN=C(C2=C1N(C=N2)C3C=C(C(C3O)O)CO)N.Cl | ||
| Formula | C12H14N4O3.HCl | M.Wt | 298.73 |
| الذوبان | ≥ 14.9mg/mL in DMSO, ≥ 18.32 mg/mL in Water with ultrasonic | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.3475 mL | 16.7375 mL | 33.475 mL |
| 5 mM | 0.6695 mL | 3.3475 mL | 6.695 mL |
| 10 mM | 0.3348 mL | 1.6738 mL | 3.3475 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *