| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
Enhancer of Zeste Homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2 (PRC2). ZLD1039 is a potent inhibitor of EZH2 with an IC50 of 5.6 nM against the wild-type enzyme. It also inhibits mutant Y641F and A677G EZH2 with IC50 values of 15 nM and 4.0 nM, respectively. The compound is highly selective for EZH2 over EZH1 (IC50 = 81 nM) and shows >4,700-fold selectivity over a panel of 14 histone methyltransferases.
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| ln Vitro |
ZLD1039 potently inhibits EZH2 methyltransferase activity with nanomolar potency. It inhibits methylation of histone 3 lysine 27 (H3K27) in MCF-7 breast cancer cells with an IC50 of 0.29 µM. At concentrations of 1 and 2 µM, it decreases expression of CDH1, CDKN1C, CDKN2A, and RUNX3 in MCF-7 cells. The compound suppresses migration of MCF-7 cells at 2 µM and inhibits cell proliferation, induces cell cycle arrest, and promotes apoptosis.
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| ln Vivo |
ZLD1039 (200 mg/kg) reduces tumor growth in MCF-7 and MDA-MB-231 mouse xenograft models. At a dose of 250 mg/kg, it inhibits tumor metastasis and decreases tumor protein levels of MMP-2, MMP-9, and E-cadherin in a 4T1 mouse xenograft model. The compound has also been shown to exert anti-inflammatory effects in cisplatin-induced acute kidney injury in mice through H3K27me3 inhibition and NF-κB pathway suppression.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for ZLD1039 typically involves measuring the enzymatic activity of recombinant EZH2 (wild-type and mutants) using a histone methyltransferase assay. The compound is incubated with the enzyme, the substrate (histone H3 peptide), and the cofactor S-adenosylmethionine (SAM). The methylation level is quantified to determine the IC50 value. Selectivity is assessed by testing the compound against EZH1 and a panel of other histone methyltransferases.
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| Cell Assay |
The in vitro cellular assay for ZLD1039 typically involves culturing breast cancer cell lines such as MCF-7 or MDA-MB-231 in appropriate growth media. Cells are treated with varying concentrations of the compound for a specified duration, and H3K27 methylation levels are measured by Western blotting or ELISA. Cell proliferation, migration, and apoptosis are assessed using standard assays such as MTT, wound healing, and flow cytometry.
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| Animal Protocol |
In vivo animal studies for ZLD1039 typically involve the use of mouse xenograft models bearing human breast tumors. Tumor-bearing mice are administered the compound via oral gavage at doses such as 200 mg/kg or 250 mg/kg. Tumor growth and metastasis are monitored over several weeks. Endpoints include tumor volume measurements, histopathological analysis, and assessment of H3K27 methylation and tumor suppressor gene expression in tumor tissues.
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| ADME/Pharmacokinetics |
ZLD1039 is orally bioavailable with favorable pharmacokinetic properties. It has a molecular weight of 612.80 g/mol and shows good solubility in DMSO (~9.09 mg/mL). The compound has a LogP of 4.5, suggesting moderate lipophilicity. It is stable at room temperature for short periods during shipping and should be stored at -20°C for long-term preservation. Further detailed PK parameters are available from the manufacturer's data sheets.
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| Toxicity/Toxicokinetics |
Specific toxicology data for ZLD1039 are not extensively reported in the public domain. The compound is intended for research use only and should be handled with appropriate laboratory safety precautions. In preclinical studies, the compound has been administered at doses up to 250 mg/kg in mice without reported severe toxicity. Comprehensive toxicity studies would be required before any clinical application.
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| References | |
| Additional Infomation |
ZLD1039 is also known as ZLD-1039 and is a promising candidate for breast cancer treatment. It acts by decreasing H3K27 methylation, leading to the up-regulation of silenced tumor suppressor genes. The compound has been shown to suppress both tumor growth and metastasis in mouse breast cancer xenograft models. It has not yet entered clinical trials and is strictly for preclinical research purposes. The molecular formula is C36H48N6O3.
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| Molecular Formula |
C36H48N6O3
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|---|---|
| Molecular Weight |
612.804728507996
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| Exact Mass |
612.378
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| Elemental Analysis |
C, 70.56; H, 7.90; N, 13.71; O, 7.83
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| CAS # |
1826865-46-6
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| PubChem CID |
132517142
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| Appearance |
Off-white to gray solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
45
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| Complexity |
1120
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C4CCCCC4=C(NC3=O)C)C5=CN=C(C=C5)N6CCN(CC6)C
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| InChi Key |
SZAYCVHJDOWSNY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C36H48N6O3/c1-5-42(28-12-18-45-19-13-28)33-21-27(26-10-11-34(37-22-26)41-16-14-40(4)15-17-41)20-31(24(33)2)35(43)38-23-32-30-9-7-6-8-29(30)25(3)39-36(32)44/h10-11,20-22,28H,5-9,12-19,23H2,1-4H3,(H,38,43)(H,39,44)
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| Chemical Name |
3-[ethyl(oxan-4-yl)amino]-2-methyl-N-[(1-methyl-3-oxo-5,6,7,8-tetrahydro-2H-isoquinolin-4-yl)methyl]-5-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]benzamide
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| Synonyms |
ZLD 1039 ZLD-1039 ZLD1039
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| HS Tariff Code |
2934.99.03.00
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 Vitro) |
DMSO : ~9.09 mg/mL (~14.83 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.91 mg/mL (1.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 9.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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: ≥ 0.91 mg/mL (1.48 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 9.1 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6319 mL | 8.1593 mL | 16.3185 mL | |
| 5 mM | 0.3264 mL | 1.6319 mL | 3.2637 mL | |
| 10 mM | 0.1632 mL | 0.8159 mL | 1.6319 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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