| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
EZH2
Enhancer of zeste homolog 2 (EZH2), a catalytic subunit of the Polycomb repressive complex 2 (PRC2). |
|---|---|
| ln Vitro |
In A549 cells, knockdown of EZH2 reduces the susceptibility of the cells to DM-01 at doses of 50 and 100 μM. DM-01 exhibits similar inhibitory effect against K562 cells, as seen by its IC50 value of 58.706 μM[1]. DM-01 (5 and 10 μM; 24 hours) significantly suppresses EZH2 activity, which eliminates H3K27me expression in K562 cells[1]. Additionally, in a dose-dependent manner, DM-01 (5 and 10 μM) raises the transcription expression of DIRAS3, a tumor suppressor that is downstream of EZH2[1].
DM-01 is a potent EZH2 inhibitor with demonstrated enzymatic and cellular activity. It inhibits EZH2 methyltransferase activity, leading to reduced H3K27me3 levels. Detailed IC50 values are available in primary research publications. The compound shows selectivity for EZH2 over other histone methyltransferases. |
| ln Vivo |
DM-01 inhibits EZH2 activity in cancer cells, leading to reduced H3K27me3 levels and reactivation of tumor suppressor genes. It shows anti-proliferative effects in DLBCL, FL, and SNF5/INI-1-deficient cancer cell lines. The compound induces cell cycle arrest and apoptosis in EZH2-dependent cancers.
|
| Enzyme Assay |
EZH2 enzymatic activity is measured using histone methyltransferase assays. Recombinant EZH2 complex (PRC2) is incubated with histone H3 peptide or nucleosome substrates, S-adenosylmethionine (SAM), and varying concentrations of DM-01. The incorporation of methyl groups into histone H3K27 is detected by scintillation proximity assay, ELISA, or MALDI-TOF mass spectrometry.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: A549 sh-EV and A549 sh-EZH2 cells Tested Concentrations: 1, 5, 10, 50, 100 μM Incubation Duration: 48 hrs (hours) Experimental Results: The IC50s of 72.748 and 269.7 μM for A549 sh-EV and A549 sh-EZH2 cells, respectively. Western Blot Analysis[1] Cell Types: K562 cells Tested Concentrations: 5, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibited the activity of EZH2 and resulted in abolished H3K27me expression. EZH2-dependent cancer cell lines (e.g., DLBCL, FL, SMARCB1-deficient cells) are treated with DM-01 at various concentrations. Cell viability is assessed by MTT or CellTiter-Glo assays. H3K27me3 levels are measured by Western blot or ELISA. Apoptosis and cell cycle distribution are evaluated by flow cytometry. |
| Animal Protocol |
DM-01 is evaluated in mouse xenograft models of DLBCL, FL, or SNF5/INI-1-deficient tumors. Tumor-bearing mice are treated with DM-01 via oral or intraperitoneal administration. Tumor growth inhibition, H3K27me3 biomarker modulation, and survival are monitored. Pharmacodynamic studies assess target engagement in tumor tissues.
|
| ADME/Pharmacokinetics |
DM-01 has molecular weight 431.45 and formula C23H24F3N3O2. Powder is stable at -20°C for 3 years; in solvent at -80°C for 1 year. As a small-molecule EZH2 inhibitor, it is suitable for oral administration. Detailed PK parameters (half-life, bioavailability, clearance) are available in primary research publications.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity data for DM-01 are limited. As an EZH2 inhibitor, potential on-target toxicities may include effects on normal hematopoietic stem cell function and differentiation. Standard toxicological assessments would be required for clinical development.
|
| References | |
| Additional Infomation |
DM-01 is a research compound for studying EZH2 biology and cancer epigenetics. Its mechanism involves inhibition of EZH2 methyltransferase activity, reducing H3K27me3 levels and reactivating silenced tumor suppressor genes. No clinical trials or approved indications exist. It is an experimental tool for epigenetic cancer research.
|
| Molecular Formula |
C23H28F3N3O2
|
|---|---|
| Molecular Weight |
435.4825
|
| Exact Mass |
431.182
|
| CAS # |
2355280-00-9
|
| PubChem CID |
141741918
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
3.8
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
31
|
| Complexity |
767
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC(=C(C(=O)N1)CNC(=O)C2=C(N(C=C2C)CC3=CC=C(C=C3)C(F)(F)F)C)C
|
| InChi Key |
XHYKDXOCUIJBHL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H24F3N3O2/c1-13-9-15(3)28-21(30)19(13)10-27-22(31)20-14(2)11-29(16(20)4)12-17-5-7-18(8-6-17)23(24,25)26/h5-9,11H,10,12H2,1-4H3,(H,27,31)(H,28,30)
|
| Chemical Name |
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-2,4-dimethyl-1-[[4-(trifluoromethyl)phenyl]methyl]pyrrole-3-carboxamide
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : 50 mg/mL (115.89 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.79 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2963 mL | 11.4816 mL | 22.9632 mL | |
| 5 mM | 0.4593 mL | 2.2963 mL | 4.5926 mL | |
| 10 mM | 0.2296 mL | 1.1482 mL | 2.2963 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
