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| 5mg |
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Purity: ≥98%
RO1138452 is a novel, potent and selective antagonist of the IP (prostacyclin) receptor. RO1138452 exhibits a strong IP receptor affinity. pKi is 9.3±0.1 in human platelets and 8.7±0.06 in a recombinant IP receptor system. RO1138452 has the ability to reduce pain and reduce inflammation. Significant reductions in acetic acid-induced abdominal constrictions are observed with RO1138452 (1-10 mg/kg, i.v.). RO1138452 (p.o., 3–100 mg/kg) dramatically lessens the mechanical hyperalgesia and edema formation caused by carrageenan. The total plasma concentration is 0.189 μg/mL one hour after rats were given RO1138452 (5 mg/kg, i.v.), while the free plasma concentration is calculated to be 0.009 μg/mL (28 nM).
| Targets |
Rat I2 Receptor ( IC50 = 7 nM ); Rat I2 Receptor ( pKi = 8.33 ); Rabbit PAF Receptor ( IC50 = 52.9 nM );
Human α2A adrenoceptor ( IC50 = 724 nM ); Rat α1B adrenoceptor ( IC50 = 3280 nM ); Human Muscarinic M4 Receptor ( IC50 = 1450 nM ); Human muscarinic M2 Receptor ( IC50 = 2220 nM ); Human muscarinic M1 Receptor ( IC50 = 2570 nM ); Human muscarinic M5 Receptor ( IC50 = 3110 nM ); Rat 5-HT1B Receptor ( IC50 = 1130 nM ); pig 5-HT2C Receptor ( IC50 = 1190 nM ); Rat 5-HT2A Receptor ( IC50 = 3040 nM ); Human 5-HT1A Receptor ( IC50 = 8580 nM ); Guinea-pig 5-HT4 Receptor ( IC50 = 8910 nM ); Rat α2Badrenoceptor ( pKi = 5.87 ); Human α2A adrenoceptor ( pKi = 6.49 ); Human muscarinic M1 Receptor ( pKi = 5.66 ); Human muscarinic M5 Receptor ( pKi = 5.81 ); Human muscarinic M2 Receptor ( pKi = 5.88 ); Human muscarinic M4 Receptor ( pKi = 6.14 ); Rabbit PAF Receptor ( pKi = 7.9 ); Guinea-pig 5-HT4 Receptor ( pKi = 5.35 ); Human 5-HT1A Receptor ( pKi = 5.37 ); Rat 5-HT2A Receptor ( pKi = 5.71 ); Rat 5-HT1B Receptor ( pKi = 6.11 ); Pig 5-HT2C Receptor ( pKi = 6.11 ) |
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| ln Vitro |
RO1138452 is IP receptor antagonist. RO1138452 has a pIC50 value of 7.0±0.07 for attenuating cAMP accumulation. By quantifying the inhibition of carbaprostacyclin-induced cAMP accumulation in CHO-K1 cells that are stable in expressing the human IP receptor, the functional antagonistic effects of RO1138452 are investigated. RO1138452's antagonist affinity (pKi) is 9.0±0.06. A panel of receptor binding and enzyme tests is used to determine the selectivity profiles for RO1138452. At imidazoline2 (I2) (8.3) and platelet activating factor (PAF) (7.9) receptors, RO1138452 exhibits affinity[1]. When added to cells in conjunction with a fixed concentration of Taprostene (1 μM), RO1138452 (10 pM–10 μM) inhibits the inhibition of CXCL9 and CXCL10 release in a concentration-dependent manner, with p[A]50 (molar) values of -8.73±0.11 and -8.47±0.16 (p>0.05), respectively[2].
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| ln Vivo |
RO1138452 has the ability to act as an analgesic and an anti-inflammatory and is a strong and selective antagonist for both rat and human IP receptors. Significant reductions in acetic acid-induced abdominal constrictions are observed with RO1138452 (1-10 mg/kg, i.v.). RO1138452 (p.o., 3–100 mg/kg) dramatically lessens the mechanical hyperalgesia and edema formation caused by carrageenan. Rats were given RO1138452 (5 mg/kg, i.v.) for one hour, during which time the total plasma concentration was 0.189 μg/mL and the free plasma concentration was calculated to be 0.009 μg/mL (28 nM)[1].
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| Enzyme Assay |
RO1138452's (10 μM) capacity to displace particular standard radioligand binding at 51 receptors is what determines its selectivity. For RO1138452, complete concentration-dependent displacement curves are constructed in triplicate and used to generate IC50 values when a significant displacement of radioligand is observed (>70%). The EP3 receptor is subjected to displacement binding. There are also experiments with enzyme inhibition. COX isoforms, namely COX-1 (ram seminal vesicle) and COX-2 (sheep placenta and human umbilical vein), are assessed for inhibition using RO1138452 at 10 μM in triplicate. The substrate utilized is arachidonic acid, and PGE2 accumulation is observed[1].
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| Cell Assay |
BEAS-2B cells are cultured in supplement-free keratinocyte serum-free medium (KSFM) with and without 100 nM RO1138452 for 30 minutes at 37°C. Following a wash in supplement-free KSFM, the cells are exposed to 1 μM Taprostene and incubated in the same medium for predetermined lengths of time. After harvesting the cells in reporter lysis buffer for four hours, luciferase activity is determined. By measuring the amount that mitochondrial dehydrogenases convert the tetrazolium salt MTT to formazan, colorimetric analysis is used to assess the viability of HAECs and BEAS-2B cells[2].
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| Animal Protocol |
Rats: RO1138452 (5 mg/kg, i.v.) is given to three male Sprague-Dawley rats. The rats are given a dose and then given 5% halothane to induce anesthesia. Blood is drawn from the rats' orbits using an orbital bleed into a syringe that has been heparinized. The blood is centrifuged at 2600× g for 5 minutes in a clinical centrifuge to extract the plasma fraction. Using high-performance liquid chromatography and mass spectrometry for detection, the amount of RO1138452 in each sample is ascertained[1].
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| References |
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| Molecular Formula |
C19H23N3O
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| Molecular Weight |
309.4054
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| Exact Mass |
309.18
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| Elemental Analysis |
C, 73.76; H, 7.49; N, 13.58; O, 5.17
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| CAS # |
221529-58-4
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| Appearance |
Solid powder
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| SMILES |
CC(C)OC1=CC=C(C=C1)CC2=CC=C(C=C2)NC3=NCCN3
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| InChi Key |
GYYRMJMXXLJZAB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H23N3O/c1-14(2)23-18-9-5-16(6-10-18)13-15-3-7-17(8-4-15)22-19-20-11-12-21-19/h3-10,14H,11-13H2,1-2H3,(H2,20,21,22)
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| Chemical Name |
N-[4-[(4-propan-2-yloxyphenyl)methyl]phenyl]-4,5-dihydro-1H-imidazol-2-amine
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| Synonyms |
RO 1138452; CAY10441; RO-1138452; RO1138452; CAY-10441; CAY 10441
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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) |
DMSO: 62~100 mg/mL (200.4~323.2 mM)
Ethanol: ~50 mg/mL (~161.6 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.08 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 25.0 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: 2.5 mg/mL (8.08 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2320 mL | 16.1598 mL | 32.3196 mL | |
| 5 mM | 0.6464 mL | 3.2320 mL | 6.4639 mL | |
| 10 mM | 0.3232 mL | 1.6160 mL | 3.2320 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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