| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
ENMD-1068 HBr primarily targets proteinase-activated receptor 2 (PAR2), a G protein-coupled receptor. It acts as an antagonist, blocking PAR2 activation by proteases such as trypsin and tryptase. By inhibiting PAR2, ENMD-1068 HBr reduces downstream signaling pathways, including MAPK and NF-κB, which are involved in inflammation and pain. The compound also attenuates joint inflammation and may modulate immune cell function.
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|---|---|
| ln Vitro |
In vitro, ENMD-1068 HBr inhibits PAR2-mediated calcium mobilization and ERK phosphorylation in cells expressing PAR2. It blocks trypsin-induced IL-6 and IL-8 release from synovial fibroblasts. ENMD-1068 HBr also inhibits PAR2-mediated proliferation and migration of cancer cells. The compound shows selectivity for PAR2 over PAR1 and PAR4.
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| ln Vivo |
In vivo, ENMD-1068 HBr reduces joint inflammation in mouse models of arthritis. It decreases swelling, inflammatory cell infiltration, and cartilage damage. The compound is administered intra-articularly or systemically. It also reduces pain in inflammatory pain models. ENMD-1068 HBr is well-tolerated at doses up to 10 mg/kg.
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| Enzyme Assay |
For receptor binding assays, membrane fractions from cells expressing PAR2 are incubated with radiolabeled PAR2 agonist in the presence of ENMD-1068 HBr. Reactions are performed in buffer containing 50 mM Tris-HCl (pH 7.4), 5 mM MgCl2, and 1 mM EDTA at 25°C for 60-120 minutes. Bound radioligand is separated by rapid filtration. For calcium mobilization assays, cells are loaded with Fluo-4 and stimulated with trypsin, and calcium flux is measured by fluorescence.
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| Cell Assay |
For cell-based assays, synovial fibroblasts or HEK293 cells expressing PAR2 are treated with ENMD-1068 HBr at 1-100 µM for 1-24 hours. IL-6 and IL-8 levels are measured by ELISA. ERK phosphorylation is assessed by Western blot. Cell proliferation is measured by MTT assay. For migration assays, cells are seeded in transwell inserts, and migration is quantified after 24 hours.
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| Animal Protocol |
For in vivo studies, mice are subjected to collagen-induced arthritis or antigen-induced arthritis. ENMD-1068 HBr is administered intra-articularly or intraperitoneally at 1-10 mg/kg daily. Joint swelling is measured, and histological analysis is performed. For pain studies, formalin or complete Freund's adjuvant models are used, and pain behavior is assessed. For pharmacokinetic studies, plasma and joint tissues are collected, and ENMD-1068 HBr is quantified by LC-MS/MS.
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| References |
| Molecular Formula |
C15H30BRN3O2
|
|---|---|
| Molecular Weight |
364.32200
|
| Exact Mass |
363.152
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| CAS # |
644961-61-5
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| Related CAS # |
ENMD-1068 hydrochloride;2703451-51-6;ENMD-1068;789488-77-3
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| PubChem CID |
9950924
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
2.756
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
21
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| Complexity |
310
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)CC(=O)N1CCN(CC1)C(=O)CCCCCN.Br
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| InChi Key |
CXPUAJQIKBLGIR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H29N3O2.BrH/c1-13(2)12-15(20)18-10-8-17(9-11-18)14(19)6-4-3-5-7-16;/h13H,3-12,16H2,1-2H3;1H
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| Chemical Name |
6-amino-1-[4-(3-methylbutanoyl)piperazin-1-yl]hexan-1-one;hydrobromide
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| Synonyms |
ENMD 1068 HBr; ENMD1068 HBr; ENMD-1068 HBr
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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|---|---|
| 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 | 2.7448 mL | 13.7242 mL | 27.4484 mL | |
| 5 mM | 0.5490 mL | 2.7448 mL | 5.4897 mL | |
| 10 mM | 0.2745 mL | 1.3724 mL | 2.7448 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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