RO1138452
Based on 1 Customer Validation
RO1138452 is a potent and selective IP (prostacyclin) receptor antagonist. RO1138452 displays high affinity for IP receptors. In human platelets, pKi is 9.3±0.1; in a recombinant IP receptor system, pKi is 8.7±0.06.
For research use only. We do not sell to patients.
- Purity: 99.26%
- CAS No.: 221529-58-4
- Formula: C19H23N3O
- Molecular Weight:309.41
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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Rat I2 Receptor 7 nM (IC50) |
Rat I2 Receptor 8.33 (pKi) |
Rabbit PAF Receptor 52.9 nM (IC50) |
Human α2A adrenoceptor 724 nM (IC50) |
Rat α1B adrenoceptor 3280 nM (IC50) |
Human Muscarinic M4 Receptor 1450 nM (IC50) |
Human muscarinic M2 Receptor 2220 nM (IC50) |
Human muscarinic M1 Receptor 2570 nM (IC50) |
Human muscarinic M5 Receptor 3110 nM (IC50) |
Rat 5-HT1B Receptor 1130 nM (IC50) |
pig 5-HT2C Receptor 1190 nM (IC50) |
Rat 5-HT2A Receptor 3040 nM (IC50) |
Human 5-HT1A Receptor 8580 nM (IC50) |
Guinea-pig 5-HT4 Receptor 8910 nM (IC50) |
Rat α1B adrenoceptor 5.87 (pKi) |
Human α2A adrenoceptor 6.49 (pKi) |
Human muscarinic M1 Receptor 5.66 (pKi) |
Human muscarinic M5 Receptor 5.81 (pKi) |
Human muscarinic M2 Receptor 5.88 (pKi) |
Human muscarinic M4 Receptor 6.14 (pKi) |
Rabbit PAF Receptor 7.9 (pKi) |
Guinea-pig 5-HT4 Receptor 5.35 (pKi) |
Human 5-HT1A Receptor 5.37 (pKi) |
Rat 5-HT2A Receptor 5.71 (pKi) |
Rat 5-HT1B Receptor 6.11 (pKi) |
Pig 5-HT2C Receptor 6.11 (pKi) |
RO1138452 is IP receptor antagonist. The pIC50 values of RO1138452 in attenuating cAMP accumulation is 7.0±0.07. Functional antagonism of RO1138452 is studied by measuring inhibition of carbaprostacyclin-induced cAMP accumulation in CHO-K1 cells stably expressing the human IP receptor. The antagonist affinity (pKi) of RO1138452 is 9.0±0.06. Selectivity profiles for RO1138452 are determined via a panel of receptor binding and enzyme assays. RO1138452 displays affinity at imidazoline2 (I2) (8.3) and platelet activating factor (PAF) (7.9) receptors[1]. RO1138452 (10 pM-10 μM) added to cells concurrently with a fixed concentration of Taprostene (1 μM) prevents, in a concentration-dependent manner, the inhibition of CXCL9 and CXCL10 release, with p[A]50 (molar) values of -8.73±0.11 and -8.47±0.16 (p>0.05), respectively[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 221529-58-4
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Appearance Solid
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Molecular Weight 309.41
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Formula C19H23N3O
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Color Light yellow to yellow
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SMILES
CC(C)OC1=CC=C(CC2=CC=C(NC3=NCCN3)C=C2)C=C1
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Synonyms
CAY10441
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Solvent & Solubility
DMSO : 100 mg/mL (323.20 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Ethanol : 50 mg/mL (161.60 mM; Need ultrasonic)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (8.08 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (8.08 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 10 mg/mL (32.32 mM); Clear solution; Need ultrasonic
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Selectivity is determined by the ability of RO1138452 (10 μM) to displace specific binding of standard radioligands at 51 receptors. When significant displacement of radioligand is observed (>70% for RO1138452), complete concentration-dependent displacement curves (in triplicate) are constructed to generate IC50 values. Displacement binding at the EP3 receptor is performed. Enzyme inhibition assays are also conducted. RO1138452 is evaluated at 10 μM in triplicate for inhibition of COX isoforms: COX-1 (ram seminal vesicle), COX-2 (sheep placenta and human umbilical vein). Arachidonic acid is used as a substrate and PGE2 accumulation is detected[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
BEAS-2B cells are incubated for 30 min at 37°C in supplement-free keratinocyte serum-free medium (KSFM) in the absence and presence of 100 nM RO1138452. Cells are washed with supplement-free KSFM, incubated in the same medium for defined periods, and exposed to 1 μM Taprostene. Four hours later, cells are harvested in reporter lysis buffer, and luciferase activity is measured. The viability HAECs and BEAS-2B cells is determined colorimetrically by measuring the reduction of the tetrazolium salt MTT to formazan, by mitochondrial dehydrogenases[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Rats[1]
Male Sprague-Dawley rats (n=3) are administered RO1138452 (5 mg/kg, i.v.). At various times after dose administration, the rats are anesthetized by halothane (5%), blood is collected by orbital bleed into a heparinized syringe and a plasma fraction is obtained by centrifugation of the blood at 2600× g for 5 min in a clinical centrifuge. The level of RO1138452 in each sample is determined by high-performance liquid chromatography with detection by mass spectrometry[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (279 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
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Handling Instructions (2659 KB)
References
[1]. Bley KR, et al. RO1138452 and RO3244794: characterization of structurally distinct, potent and selective IP (prostacyclin) receptor antagonists. Br J Pharmacol. 2006 Feb;147(3):335-45. [Content Brief]
[2]. Ayer LM, et al. 4,5-Dihydro-1H-imidazol-2-yl)-[4-(4-isopropoxy-benzyl)-phenyl]-amine (RO1138452) is a selective, pseudo-irreversible orthosteric antagonist at the prostacyclin (IP)-receptor expressed by human airway epithelial cells: IP-receptor-mediated inhibition of CXCL9 and CXCL10 release. J Pharmacol Exp Ther. 2008 Feb;324(2):815-26. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| Ethanol / DMSO | 1 mM | 3.2320 mL | 16.1598 mL | 32.3196 mL | 80.7989 mL |
| 5 mM | 0.6464 mL | 3.2320 mL | 6.4639 mL | 16.1598 mL | |
| 10 mM | 0.3232 mL | 1.6160 mL | 3.2320 mL | 8.0799 mL | |
| 15 mM | 0.2155 mL | 1.0773 mL | 2.1546 mL | 5.3866 mL | |
| 20 mM | 0.1616 mL | 0.8080 mL | 1.6160 mL | 4.0399 mL | |
| 25 mM | 0.1293 mL | 0.6464 mL | 1.2928 mL | 3.2320 mL | |
| 30 mM | 0.1077 mL | 0.5387 mL | 1.0773 mL | 2.6933 mL | |
| 40 mM | 0.0808 mL | 0.4040 mL | 0.8080 mL | 2.0200 mL | |
| 50 mM | 0.0646 mL | 0.3232 mL | 0.6464 mL | 1.6160 mL | |
| 60 mM | 0.0539 mL | 0.2693 mL | 0.5387 mL | 1.3466 mL | |
| 80 mM | 0.0404 mL | 0.2020 mL | 0.4040 mL | 1.0100 mL | |
| 100 mM | 0.0323 mL | 0.1616 mL | 0.3232 mL | 0.8080 mL |
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