| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
EPZ031686 selectively targets SMYD3, a lysine methyltransferase that methylates histone H3 at lysine 4 (H3K4) and non-histone proteins such as MAP3K2 (MEKK2). In biochemical assays, it inhibits SMYD3 with an IC₅₀ of 3 nM and acts as a non-competitive inhibitor with respect to both SAM and the protein substrate MEKK2. It displays a Ki of 1.2 nM for SMYD3 and 1.1 nM for MEKK2. The compound shows <30% inhibition against 16 histone methyltransferase targets at 10 µM.
|
|---|---|
| ln Vitro |
In vitro, EPZ031686 potently inhibits SMYD3 with an IC₅₀ of 3 nM in biochemical assays. It displays a Ki of 1.2 nM for SMYD3 and 1.1 nM for MEKK2. In cellular assays, the compound shows an IC₅₀ of 36 nM, making it the first SMYD3 inhibitor with double-digit nanomolar cellular activity. It demonstrates <30% inhibition against 16 histone methyltransferase targets at 10 µM, indicating high selectivity.
|
| ln Vivo |
In vivo, EPZ031686 shows good oral bioavailability in mice (F = 48-69%), enabling repeated dosing without injection stress. The compound's oral bioavailability and favorable ADME profile support in vivo target engagement studies. It serves as a gold-standard reference for benchmarking novel SMYD3 inhibitors in cellular assays. The compound's non-competitive binding mode supports assay robustness under varying substrate levels.
|
| Enzyme Assay |
Non-cellular enzyme assays for EPZ031686 involve assessing its inhibition of SMYD3 methyltransferase activity using purified recombinant SMYD3 enzyme. The enzyme is incubated with a peptide substrate (e.g., histone H4) and the methyl donor S-adenosylmethionine (SAM) in the presence of varying concentrations of EPZ031686. The incorporation of methyl groups into the substrate is measured using a radiometric assay with [³H]-SAM or using a luminescence-based assay (e.g., MTase-Glo™). IC₅₀ and Ki values are determined from dose-response curves.
|
| Cell Assay |
In vitro cellular assays for EPZ031686 involve treating cancer cell lines with the compound and assessing cell viability, proliferation, and SMYD3 activity. Cells are treated with varying concentrations of EPZ031686 for 72-120 hours. Cell viability is measured using MTT or CellTiter-Glo® assays. SMYD3 activity is assessed by measuring H3K4 methylation levels by Western blotting using a methylation-specific antibody. The compound's effects on downstream target gene expression are evaluated by qPCR.
|
| Animal Protocol |
In vivo animal experiments with EPZ031686 are conducted in mouse models of cancer. Tumor-bearing mice are treated with EPZ031686 via oral gavage at various doses. Tumor growth inhibition is monitored by caliper measurements. At study termination, tumors are collected for assessment of SMYD3 activity and downstream signaling by immunohistochemistry or Western blotting. Pharmacokinetic studies characterize absorption, distribution, and systemic exposure.
|
| ADME/Pharmacokinetics |
EPZ031686 has a molecular weight of 591.09 and a molecular formula of C₂₆H₃₄ClF₃N₄O₄S. It is a solid powder with a purity of ≥98%. The compound is soluble in DMSO. For short-term storage (days to weeks), it should be kept dry, dark, and at 0-4°C; for long-term storage (months to years), it should be stored at -20°C. It is stable under recommended storage conditions.
|
| Toxicity/Toxicokinetics |
EPZ031686 is a research compound for laboratory use only and is not approved for human therapeutic use. In preclinical studies, it has been generally well-tolerated at therapeutic doses. Standard laboratory safety precautions should be followed when handling the compound. It may cause skin, eye, and respiratory irritation. Appropriate personal protective equipment should be used.
|
| References |
[2] Therapeutical potential of deregulated\nlysine methyltransferase SMYD3 as a safe target for novel anticancer agents.\nExpert Opin Ther Targets. 2017 Feb;21(2):145-157. |
| Additional Infomation |
EPZ031686 (CAS 1808011-22-4) is a potent, selective, and orally bioavailable SMYD3 inhibitor with a biochemical IC₅₀ of 3 nM and a cellular IC₅₀ of 36 nM. It displays a Ki of 1.2 nM for SMYD3 and 1.1 nM for MEKK2. The compound shows good oral bioavailability in mice (F = 48-69%) and is the first SMYD3 inhibitor with double-digit nanomolar cellular activity. It is used as a research tool for studying SMYD3 function in cancer biology.
|
| Molecular Formula |
C26H34CLF3N4O4S
|
|---|---|
| Molecular Weight |
591.0872
|
| Exact Mass |
590.194
|
| CAS # |
1808011-22-4
|
| Related CAS # |
1808011-22-4
|
| PubChem CID |
118946372
|
| Appearance |
White to light yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Index of Refraction |
1.603
|
| LogP |
3.44
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
39
|
| Complexity |
1000
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C1C[C@H]2CC(C[C@@H]1N2S(=O)(=O)CC3CCN(CC3)CCCC(F)(F)F)NC(=O)C4=C(C=C5C(=C4)CC(=O)N5)Cl
|
| InChi Key |
OTEIUEJPHNOGBG-ACDBMABISA-N
|
| InChi Code |
InChI=1S/C26H34ClF3N4O4S/c27-22-14-23-17(11-24(35)32-23)10-21(22)25(36)31-18-12-19-2-3-20(13-18)34(19)39(37,38)15-16-4-8-33(9-5-16)7-1-6-26(28,29)30/h10,14,16,18-20H,1-9,11-13,15H2,(H,31,36)(H,32,35)/t18-,19+,20-
|
| Chemical Name |
6-chloro-2-oxo-N-((1R,3r,5S)-8-(((1-(4,4,4-trifluorobutyl)piperidin-4-yl)methyl)sulfonyl)-8-azabicyclo[3.2.1]octan-3-yl)indoline-5-carboxamide
|
| Synonyms |
EPZ-031686 EPZ031686 EPZ 031686.
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6918 mL | 8.4589 mL | 16.9179 mL | |
| 5 mM | 0.3384 mL | 1.6918 mL | 3.3836 mL | |
| 10 mM | 0.1692 mL | 0.8459 mL | 1.6918 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
COA