| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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Purity: ≥98%
IPSU is a novel, potent, selective, orally bioavailable and brain penetrant orexin receptor (OX2R) antagonist with potential to be used for insomnia. It inhibits OX2R with a pKi of 7.85. IPSU binds quickly and reaches equilibrium in assays for binding and/or functionality very quickly. In general, IPSU has a slow rate of equilibrium convergence and a tendency to be relatively unselective in non-equilibrium situations. Every ligand exhibits a selectivity profile when equilibrium is reached, which differs from the non-equilibrium state. The 'dual' antagonists tested have slow kinetics, which implies that the duration of in vitro receptor occupancy might be longer than anticipated. This raises concerns about the accuracy of pharmacokinetic studies measuring these antagonists' brain or plasma levels as indicators of receptor occupancy in vivo.
| Targets |
OX2R ( pKi = 7.85 ); OX1R ( pKi = 6.29 )
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
One concentration of radioligand and six concentrations of competitors (unlabeled ligands such as BBAC, almorexant, SB-649868, suvorexant, filorexant, or IPSU) are used in competition experiments. Membranes (150 μL/well) are filled to capacity with 4.6 nM [3H]-BBAC and different concentrations of unlabeled ligand (0.1 nM–10 μM) in 50 μL/well of assay buffer, for a total volume of 250 μL/well. At room temperature, the amount of [3H]-BBAC bound to receptors is measured at various time intervals (from 15 min to 4 h), and the process is concluded by liquid scintillation counting and fast vacuum filtration[2].
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| Animal Protocol |
Mice: C57Bl/6 mice that are allowed to roam freely and have permanent electrode implantations are accustomed to the experiment boxes and have unlimited access to food and drink. Just before lights out and recording begins, the test compounds (IPSU) or vehicle are given one at a time as a suspension in 0.5% methylcellulose. Infrared sensors installed in the box's roof record movement. To categorize 10 s epochs into wake, NREM sleep, and REM sleep, EEG/EMG signals and motility data are utilized. By applying and recording the vehicle the day before compound (IPSU) dosing, each animal acted as its own control[1].
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| References |
| Molecular Formula |
C23H27N5O2
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| Molecular Weight |
405.50
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| Exact Mass |
405.216
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| Elemental Analysis |
C, 68.13; H, 6.71; N, 17.27; O, 7.89
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| CAS # |
1373765-19-5
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| Related CAS # |
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| PubChem CID |
56970858
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
702.0±70.0 °C at 760 mmHg
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| Flash Point |
378.4±35.7 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.674
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| LogP |
3.92
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
608
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C2(C([H])([H])C([H])([H])N(C3=NC([H])=C([H])C(=N3)OC([H])([H])[H])C([H])([H])C2([H])[H])C([H])([H])C([H])([H])C([H])([H])N1C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12
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| InChi Key |
PCMHOSYCWRRHTG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H27N5O2/c1-30-20-7-11-24-22(26-20)27-13-9-23(10-14-27)8-4-12-28(21(23)29)16-17-15-25-19-6-3-2-5-18(17)19/h2-3,5-7,11,15,25H,4,8-10,12-14,16H2,1H3
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| Chemical Name |
2-(1H-indol-3-ylmethyl)-9-(4-methoxypyrimidin-2-yl)-2,9-diazaspiro[5.5]undecan-1-one
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| Synonyms |
IPSU
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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 |
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| 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) |
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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 | 2.4661 mL | 12.3305 mL | 24.6609 mL | |
| 5 mM | 0.4932 mL | 2.4661 mL | 4.9322 mL | |
| 10 mM | 0.2466 mL | 1.2330 mL | 2.4661 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.
Effect of time on IPSU competition for [3H]-BBAC ((S)-N-([1,1′-biphenyl]-2-yl)-1-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2-carboxamide) binding to membranes from CHO cells expressing human (A) OX1R or (B) OX2R.Front Neurosci.2013 Dec 3;7:230. |
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