| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
RG 12525 primarily targets the Leukotriene Receptor (CysLT1), PPAR-γ (Peroxisome Proliferator-Activated Receptor gamma), and the cytochrome P450 enzyme CYP3A4. It acts as an antagonist at the leukotriene receptor and an agonist at PPAR-γ.
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| ln Vitro |
RG 12525 selectively and more than 8000 times antagonizes the spasmodic actions of LTC4, LTD4, and LTE4 on lung strips (KB value = 3 nM) and competitively inhibits the binding of 3H-LTD4 to lung membranes (Ki = 3.0 +/- 0.3 nM)[1]. RG 12525 (at 2.5 µM or 25 µM) suppresses CYP2C9 and -3A4 microsomal activity, but not CYP1A2, -2A6, -2C19, or -2D6. At 5 and 10 µM midazolam doses, RG 12525 (25 µM) likewise significantly inhibits [2].
In cell-free assays, RG 12525 competitively inhibits the binding of 3H-LTD4 to lung membranes with a Ki of 3.0 ± 0.3 nM. It antagonizes the spasmogenic activity of LTC4, LTD4, and LTE4 on lung strips with KB values of 3 nM. Furthermore, it suppresses CYP2C9 and CYP3A4 microsomal activity at concentrations of 2.5 µM or 25 µM. |
| ln Vivo |
ORAL RG 12525 suppresses bronchoconstriction (ED50 = 0.6 mg/kg), wheal development (ED50 = 5 mg/kg, 9 mg/kg t1/2 = 10 hours), anaphylaxis mortality (ED50 = 2.2 mg)/kg, t1/2 = 7 hours (10 mg/kg), and antigen-induced bronchoconstriction (ED50 = 0.6 mg/kg) [1]. In an anaphylaxis paradigm, RG 12525 decreases antigen-induced mortality; ED50 (95% confidence interval) = 2.2 (0.8-6.4) mg/kg. RG 12525 also reduced LTD4-induced bronchoconstriction with an ED50 = 0.6 (0.4-1.0) mg/kg in a lung function model[3].
Orally administered RG 12525 suppresses bronchoconstriction (ED50 = 0.6 mg/kg) and LTD4-induced wheal development (ED50 = 5 mg/kg). In an anaphylaxis model, it reduces antigen-induced mortality with an ED50 of 2.2 mg/kg. It also inhibits antigen-induced bronchoconstriction, with a half-life (t1/2) of 7 hours at a 10 mg/kg dose and 10 hours at a 9 mg/kg dose. |
| Enzyme Assay |
The standard assay involves preparing membrane fractions from lung tissue and incubating them with a radiolabeled ligand such as 3H-LTD4 in the presence of varying concentrations of RG 12525. Non-specific binding is determined using an excess of unlabeled ligand. After incubation, the mixture is filtered through glass fiber filters and washed. The bound radioactivity is then measured using a scintillation counter to calculate the inhibition constant (Ki).
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| Cell Assay |
For cellular assays, cell lines expressing the target receptors, such as those from guinea pig lung parenchyma, are cultured in appropriate media. Cells are pre-incubated with various concentrations of RG 12525 before being stimulated with agonists like LTC4, LTD4, or LTE4. The induced contraction is measured as a functional readout. The concentration of compound required to inhibit 50% of the maximal response (IC50) is then determined.
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| Animal Protocol |
In animal models, RG 12525 is typically administered orally to rodents or guinea pigs. For bronchoconstriction studies, the compound is given as a pretreatment, followed by challenge with an antigen or agonist like LTD4. The effective dose required to inhibit 50% of the bronchoconstriction (ED50) is then calculated. In anaphylaxis models, survival rates are monitored following antigen challenge, and the ED50 for preventing mortality is determined.
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| ADME/Pharmacokinetics |
RG 12525 is orally bioavailable. Following oral administration, it exhibits a half-life (t1/2) of approximately 10 hours at a 9 mg/kg dose and 7 hours at a 10 mg/kg dose in animal models. The compound has a LogP of 4.496.
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| Toxicity/Toxicokinetics |
RG 12525 is an inhibitor of CYP3A4, with a Ki value of 0.5 µM. It also suppresses CYP2C9 microsomal activity. At higher concentrations (25 µM), it has been shown to inhibit midazolam metabolism, indicating potential for drug-drug interactions.
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| References |
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| Additional Infomation |
RG 12525 has been studied for its potential in treating asthma and other inflammatory conditions due to its role as a leukotriene receptor antagonist. However, it has not been clinically advanced for this indication and remains primarily a research tool. Its additional role as a PPAR-γ agonist suggests potential applications in metabolic research.
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| Molecular Formula |
C25H21N5O2
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|---|---|
| Molecular Weight |
423.47
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| Exact Mass |
423.17
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| CAS # |
120128-20-3
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| PubChem CID |
129044
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| Appearance |
White to yellow solid powder
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| Density |
1.308g/cm3
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| Boiling Point |
667ºC at 760 mmHg
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| Flash Point |
227.3ºC
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| Vapour Pressure |
1.17E-17mmHg at 25°C
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| Index of Refraction |
1.681
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| LogP |
4.496
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
32
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| Complexity |
559
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
JELDFLOBXROBFH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H21N5O2/c1-2-7-20(19(6-1)15-25-27-29-30-28-25)16-31-22-11-13-23(14-12-22)32-17-21-10-9-18-5-3-4-8-24(18)26-21/h1-14H,15-17H2,(H,27,28,29,30)
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| Chemical Name |
2-[[4-[[2-(2H-tetrazol-5-ylmethyl)phenyl]methoxy]phenoxy]methyl]quinoline
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| Synonyms |
RG12525; RG-12525; RG 12525
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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 : ~25 mg/mL (~59.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.91 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 (4.91 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3614 mL | 11.8072 mL | 23.6144 mL | |
| 5 mM | 0.4723 mL | 2.3614 mL | 4.7229 mL | |
| 10 mM | 0.2361 mL | 1.1807 mL | 2.3614 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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