| Size | Price | Stock | Qty |
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| 10mg |
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| Other Sizes |
| Targets |
ENMD-1068 targets protease-activated receptor 2 (PAR2), a G protein-coupled receptor that is activated by proteolytic cleavage and is involved in inflammation, pain, angiogenesis, and fibrosis. By acting as a selective antagonist at PAR2, ENMD-1068 blocks PAR2-mediated signaling pathways. The compound reduces hepatic stellate cell activation and collagen expression through the inhibition of TGF-β1/Smad signal transduction. ENMD-1068 also inhibits the proliferation of endometrial cells and induces apoptosis in lesional epithelial cells.
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| ln Vitro |
EnMD-1068 (10 mM; 24 hours) reduces the release of calcium from HSCs induced by trypsin or SLIGRL-NH2. TGF-β1/Smad signaling is important for HSC activation and collagen synthesis. ENMD-1068 (10 mM) prevents this signaling in primary HSCs [1].
In vitro, ENMD-1068 HCl acts as a selective antagonist at PAR2 with an IC50 of 5000 μM. It reduces hepatic stellate cell activation and collagen expression by inhibiting TGF-β1/Smad signaling. The compound inhibits the proliferation of endometrial cells and induces apoptosis in lesional epithelial cells. These in vitro studies confirm the compound's anti-inflammatory, anti-fibrotic, and anti-angiogenic activities. ENMD-1068 HCl has also been used to determine the pathway responsible for paw edema induced by venom serine protease. |
| ln Vivo |
Mice's liver fibrosis is inhibited by ENMD-1068 (25, 50 mg/kg; intraperitoneal injection; twice weekly for 4 weeks) [1]. One intraperitoneal injection of ENMD-1068 (25, 50 mg/kg) administered once daily for five days suppresses the proliferation of platelets controlled by endometriosis and dose-dependently lowers MCP-1 and IL-6 levels [2]. lasting five days) will cause mice's cell transplantation index to rise and their epithelial cell swelling to decrease [2].
In vivo, ENMD-1068 HCl has demonstrated efficacy in animal models. It inhibits the development of endometriosis in a mouse model. The compound has been used as a PAR2 antagonist to determine the pathway responsible for paw edema induced by Crotalus durissus terrificus venom serine protease (Cdtsp 2). ENMD-1068 HCl's anti-angiogenic and anti-inflammatory activities support its potential for treating endometriosis and fibrotic diseases. Further in vivo studies would be required to fully characterize its therapeutic potential. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for ENMD-1068 HCl are radioligand binding assays using membrane preparations from cells expressing recombinant human PAR2. The compound's binding affinity is determined by its ability to displace a labeled PAR2 ligand. Functional assays such as calcium mobilization assays can also be used to measure the compound's antagonist activity at PAR2. The IC50 for inhibition of PAR2-mediated signaling is determined from dose-response curves. These assays confirm the compound's selective PAR2 antagonism.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Hepatic stellate cells (HSC) (stimulated by TGF-β1) Tested Concentrations: 10 mM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibition of TGF-β1-induced α-SMA, Col α1(І), Col Expression of α1(III) and Smad2/3 C-terminal phosphorylation. In vitro cellular assays for ENMD-1068 HCl are performed using various cell types, including hepatic stellate cells, endometrial cells, and other PAR2-expressing cells. Cells are treated with ENMD-1068 HCl and stimulated with PAR2 agonists (e.g., trypsin or SLIGRL peptide). Calcium mobilization is measured using fluorescent calcium indicators to assess PAR2 activation. Hepatic stellate cell activation is assessed by measuring collagen expression and TGF-β1/Smad signaling by Western blotting or quantitative PCR. Endometrial cell proliferation is measured using MTT assays, and apoptosis is evaluated using annexin V staining. |
| Animal Protocol |
Animal/Disease Models: ICR mouse (8 weeks old; CCl4-induced liver fibrosis model) [1].
Doses: 25, 50 mg/kg Route of Administration: intraperitoneal (ip) injection; twice a week for 4 weeks. Experimental Results: Collagen deposition was Dramatically weakened. Animal/Disease Models: Mice with surgically induced endometriosis [2]. Doses: 25, 50 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 5 days Experimental Results: Reduction in observed lesion volume in a dose-dependent manner. Inhibits the expression of IL-6 and MCP-1. Reduce the proliferation rate of endometriotic cells and increase the percentage of apoptotic epithelial cells in the lesions. In vivo animal experiments for ENMD-1068 HCl have been conducted in mouse models of endometriosis and inflammation. In the endometriosis model, mice are administered ENMD-1068 HCl via intraperitoneal or oral administration, and the development of endometriotic lesions is assessed. In the paw edema model, mice are injected with venom serine protease, and paw swelling is measured in the presence or absence of ENMD-1068 HCl. These studies evaluate the compound's efficacy in reducing inflammation and disease progression. |
| ADME/Pharmacokinetics |
ENMD-1068 HCl has a molecular weight of 283.41 g/mol and a molecular formula of C15H29N3O2. The compound is soluble in DMSO at concentrations up to 245 mg/mL (864.47 mM). For in vivo administration, it can be formulated in 10% DMSO + 90% Saline at concentrations up to 10 mg/mL (35.28 mM). The compound is stable as a pure form at -20°C for up to 3 years and in solution at -80°C for up to 1 year. Detailed pharmacokinetic properties have not been extensively reported.
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| Toxicity/Toxicokinetics |
ENMD-1068 HCl has been evaluated in preclinical studies and has been reported to be well-tolerated at effective doses. No significant toxicity has been reported in the available literature. As a selective PAR2 antagonist, ENMD-1068 HCl may have a favorable safety profile with reduced risk of off-target effects. However, comprehensive toxicology studies would be necessary to fully assess the compound's safety for clinical development. The compound is a research tool for studying PAR2 biology.
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| References |
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| Additional Infomation |
ENMD-1068 HCl is a selective protease-activated receptor 2 (PAR2) antagonist with anti-angiogenic and anti-inflammatory activities. It reduces hepatic stellate cell activation and collagen expression by inhibiting TGF-β1/Smad signaling. ENMD-1068 HCl inhibits the proliferation of endometrial cells, induces apoptosis in lesional epithelial cells, and inhibits the development of endometriosis in a mouse model. The compound is a research tool for studying PAR2 biology and is not an approved drug.
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| Molecular Formula |
C15H30CLN3O2
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| Molecular Weight |
319.874
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| Exact Mass |
283.226
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| CAS # |
789488-77-3
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| Related CAS # |
ENMD-1068 hydrochloride;2703451-51-6;ENMD-1068 hydrobromide;644961-61-5
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| PubChem CID |
9950925
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| Appearance |
White to off-white solid powder
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| LogP |
1.798
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
20
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| Complexity |
310
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)CC(=O)N1CCN(CC1)C(=O)CCCCCN.Cl
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| InChi Key |
VRZYMMVEALDDBH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H29N3O2/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
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| Chemical Name |
6-amino-1-[4-(3-methylbutanoyl)piperazin-1-yl]hexan-1-one
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| Synonyms |
ENMD 1068; ENMD-1068; ENMD1068
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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 | 3.1263 mL | 15.6314 mL | 31.2627 mL | |
| 5 mM | 0.6253 mL | 3.1263 mL | 6.2525 mL | |
| 10 mM | 0.3126 mL | 1.5631 mL | 3.1263 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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