| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
The compound targets the EED (Embryonic Ectoderm Development) protein, which is a core component of the Polycomb Repressive Complex 2 (PRC2). PRC2 is a histone methyltransferase responsible for the trimethylation of histone H3 at lysine 27 (H3K27me3), an epigenetic mark that silences gene expression. By binding to EED, EEDi-5273 disrupts the allosteric activation of the PRC2 complex, leading to the global reduction of H3K27me3 and the re-expression of silenced genes.
|
|---|---|
| ln Vitro |
In biochemical assays, EEDi-5273 demonstrates an IC50 of 0.2 nM against EED, indicating exceptionally high potency. This inhibition effectively blocks the activity of the PRC2 complex and prevents the establishment of the repressive H3K27me3 mark. The compound shows superior activity compared to earlier generation EZH2 and EED inhibitors, and is able to achieve complete and persistent regression of tumors in certain cancer models.
|
| ln Vivo |
As an exceptionally potent and orally efficacious EED inhibitor, EEDi-5273 shows strong anti-tumor activity in various pre-clinical mouse models of cancer, such as lymphoma, leukemia, and solid tumors. It is capable of achieving complete and sustained tumor regression, often at well-tolerated dose levels. The compound is being investigated for its utility in treating PRC2-driven cancers and non-cancer indications such as hemoglobinopathies.
|
| Enzyme Assay |
The biochemical assay for EED inhibitors typically involves an AlphaScreen or TR-FRET method to measure the binding to EED. Biotinylated EED protein is mixed with a labeled histone H3K27me3 peptide (the natural ligand for EED) and varying concentrations of EEDi-5273. The proximity of the donor and acceptor beads is used to measure the disruption of the EED-peptide interaction, allowing for the calculation of the IC50 for competitive binding to the EED protein.
|
| Cell Assay |
In a cellular assay, PRC2-dependent cancer cells (e.g., KARPAS-422 lymphoma or G401 rhabdoid tumor cells) are treated with varying concentrations of EEDi-5273 for 3-7 days. Cell viability is measured using a CellTiter-Glo luminescent assay to determine the IC50 for growth inhibition. The pharmacodynamic effect is assessed by treating cells for 3-5 days and then analyzing the levels of H3K27me3, total H3, and EZH2 by Western blot. Global gene expression changes are analyzed by RNA sequencing.
|
| Animal Protocol |
In vivo efficacy is typically evaluated in a xenograft mouse model of KARPAS-422 lymphoma. Athymic nude mice bearing established subcutaneous tumors (~150-200 mm3) are randomized into treatment groups. EEDi-5273 is administered via oral gavage daily at dose levels such as 3, 10, and 30 mg/kg. Tumor volume is measured twice weekly by calipers to calculate the tumor growth inhibition (TGI). At the end of the study, tumors are excised and analyzed for H3K27me3 levels by immunohistochemistry and Western blot to confirm target engagement.
|
| ADME/Pharmacokinetics |
EEDi-5273 is an orally bioavailable inhibitor. While specific quantitative PK parameters for this compound are not provided in the search results, its classification as an “orally efficacious” compound indicates it has favorable drug-like properties, including sufficient oral absorption, metabolic stability, and systemic exposure to achieve a durable pharmacodynamic effect in vivo (e.g., sustained reduction of H3K27me3).
|
| Toxicity/Toxicokinetics |
Specific toxicological data for EEDi-5273 are not detailed. As an epigenetic inhibitor of the PRC2 complex, potential toxicities could include effects on normal differentiation processes in the gut and bone marrow, which are common class-based observations for PRC2 inhibitors. However, its potent on-target activity and favorable in vivo tolerability profile observed in pre-clinical studies suggest a potentially manageable safety window.
|
| References | |
| Additional Infomation |
EEDi-5273 is a next-generation, research-grade chemical that targets the PRC2 complex by a novel mechanism-disrupting the EED-histone H3K27me3 interaction, rather than directly inhibiting the EZH2 enzyme. This mechanism may provide advantages, including a potential for greater selectivity and a different resistance profile. As of the latest updates, this compound is a powerful pre-clinical research tool and has not yet been approved for clinical use.
|
| Molecular Formula |
C26H22F4N6O2
|
|---|---|
| Molecular Weight |
526.49
|
| Exact Mass |
526.174
|
| CAS # |
2585648-55-9
|
| PubChem CID |
155580034
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
4.8
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
38
|
| Complexity |
879
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1C=CC2=C(CCO2)C=1CNC1=NC=C2C3=CN=C(C(F)(F)F)C=C3CN(C(C3=C2N1C=N3)=O)C(C)C
|
| InChi Key |
OAYMRNSLBKYMKG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H22F4N6O2/c1-13(2)35-11-14-7-21(26(28,29)30)31-8-16(14)18-10-33-25(36-12-34-22(23(18)36)24(35)37)32-9-17-15-5-6-38-20(15)4-3-19(17)27/h3-4,7-8,10,12-13H,5-6,9,11H2,1-2H3,(H,32,33)
|
| Chemical Name |
15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-9-propan-2-yl-5-(trifluoromethyl)-4,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,11(18),12,15-heptaen-10-one
|
| 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 : ~25 mg/mL (~47.48 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (1.90 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8994 mL | 9.4969 mL | 18.9937 mL | |
| 5 mM | 0.3799 mL | 1.8994 mL | 3.7987 mL | |
| 10 mM | 0.1899 mL | 0.9497 mL | 1.8994 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
