| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
AR-9281 targets soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). It acts as a potent and selective inhibitor. It inhibits HsEH and MsEH with IC50 values of 13.8 nM and 1.7 nM, respectively. By inhibiting sEH, it increases the levels of EETs, which have anti-inflammatory and vasodilatory effects.
|
|---|---|
| ln Vitro |
AR-9281 (APAU), with IC50 values of 13.8 nM and 1.7 nM, respectively, has inhibitory efficacy against human sEH (HsEH) and murine sEH (MsEH)[1].
In vitro, AR-9281 has inhibitory activity for human sEH (HsEH) and murine sEH (MsEH) with IC50 values of 13.8 nM and 1.7 nM, respectively. It is a potent and selective inhibitor of sEH. These activities confirm its profile as a potent sEH inhibitor. |
| ln Vivo |
AR-9281 (APAU) (oral, 150-200 mg/dL for 6 weeks) increases the therapeutic impact of EETs, slows the progression of hyperglycemia, protects myocyte structure, and lowers Ca2+ dysregulation and SERCA remodeling in hyperglycemic rats [2] .
In vivo, AR-9281 has been investigated for use/treatment in hypertension. It can be used for the research of inflammation, hypertension, and type 2 diabetes. By inhibiting sEH and increasing EET levels, it may exert vasodilatory and anti-inflammatory effects. However, specific details of in vivo efficacy studies are not extensively detailed in the available literature. |
| Enzyme Assay |
The in vitro enzyme assay for AR-9281 measures its ability to inhibit soluble epoxide hydrolase activity. These cell-free assays use purified sEH and a fluorogenic substrate. The compound's inhibitory potency (IC50) is determined by measuring the reduction in enzyme activity. AR-9281 shows IC50 values of 13.8 nM for HsEH and 1.7 nM for MsEH.
|
| Cell Assay |
In vitro cellular assays for AR-9281 assess its effects on EET metabolism and downstream signaling. Cells are treated with AR-9281, and the levels of EETs and DHETs are measured. Its effects on inflammation and vascular function can also be assessed in cellular models. These assays demonstrate the compound's functional activity in a relevant cellular context.
|
| Animal Protocol |
Animal/Disease Models: T2DM rat model [2]
Doses: 150-200 mg/dL Route of Administration: Oral (drinking) for 6 weeks Experimental Results: Attenuated the progressive increase in blood glucose concentration and preserved the mitochondrial structure and myogen of cardiomyocytes Fiber morphology. Protect intracellular Ca2+ effector system. There was less downregulation of sarco(end)oplasmic reticulum Ca2+ ATPase (SERCA) and lower expression of hypertrophy markers. In vivo animal studies for AR-9281 have been conducted in models of hypertension, inflammation, and type 2 diabetes to evaluate its efficacy. However, specific details of these studies are not extensively detailed in the available literature. It is a research compound and is not approved for clinical use. |
| ADME/Pharmacokinetics |
AR-9281 is orally active. Its pharmacokinetic properties support oral administration. As a small molecule, it is absorbed and distributed throughout the body. However, detailed parameters such as half-life and bioavailability are not extensively detailed in the available literature. It is intended for research use only.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for AR-9281 are not extensively detailed in the available literature. As a sEH inhibitor, its toxicity profile is likely related to its mechanism of action. However, it has been investigated in clinical studies for hypertension, indicating a manageable safety profile. It is intended for research purposes only.
|
| References |
|
| Additional Infomation |
AR-9281 inhibits soluble epoxide hydrolase.
Drug Indications It has been studied for the treatment of hypertension. Mechanism of Action AR9281 inhibits soluble epoxide hydrolase (s-EH), an enzyme that plays a key role in the cytochrome P450 pathway of arachidonic acid metabolism. Nuclear factor αB (NF-αB) is a transcription factor associated with cardiac hypertrophy and can exert anti-apoptotic or pro-apoptotic effects under various conditions. Epoxyeicosatotrienoic acid (EETs) are products of cytochrome P450 epoxides and possess various antihypertensive and anti-inflammatory effects. EETs have a vasodilatory effect similar to endothelial hyperpolarizing factor and may inhibit NF-αB through a currently unknown mechanism. s-EH enzymes catalyze the degradation of EETs into dihydroxyeicosatotrienoic acid. AR9281 enhances the antihypertensive and anti-inflammatory activities of EETs by inhibiting s-EH, preventing s-EH from breaking down EETs, and inhibiting NF-αB. AR-9281 is a potent, selective, and orally active inhibitor of soluble epoxide hydrolase (sEH). It has been investigated for the treatment of hypertension, inflammation, and type 2 diabetes. It is a research compound and is not approved for clinical use. |
| Molecular Formula |
C18H29N3O2
|
|---|---|
| Molecular Weight |
319.441764593124
|
| Exact Mass |
319.225
|
| CAS # |
913548-29-5
|
| Related CAS # |
913548-29-5;
|
| PubChem CID |
12000797
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.1
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
23
|
| Complexity |
455
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(NC12CC3CC(C1)CC(C3)C2)NC1CCN(C(C)=O)CC1
|
| InChi Key |
HUDQLWBKJOMXSZ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H29N3O2/c1-12(22)21-4-2-16(3-5-21)19-17(23)20-18-9-13-6-14(10-18)8-15(7-13)11-18/h13-16H,2-11H2,1H3,(H2,19,20,23)
|
| Chemical Name |
1-(1-acetylpiperidin-4-yl)-3-(1-adamantyl)urea
|
| 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 (~78.26 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1305 mL | 15.6524 mL | 31.3048 mL | |
| 5 mM | 0.6261 mL | 3.1305 mL | 6.2610 mL | |
| 10 mM | 0.3130 mL | 1.5652 mL | 3.1305 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00847899 | Completed | Drug: AR9281 Drug: AR9281 Drug: Placebo Drug: Placebo |
Hypertension Impaired Glucose Tolerance |
Arete Therapeutics | 2009-01 | Phase 2 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
