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Purity: ≥98%
AM-0902 is a novel, potent and selective Transient Receptor Potential A1 (TRPA1) antagonist with IC50s of 71 and 131 nM for rTRPA1 and hTRPA1, respectively. AM-0902 demonstrated dose-dependent inhibition of AITC-induced flinching in rats, validating its utility as a tool for interrogating the role of TRPA1 in in vivo pain models.
| ln Vitro |
IC50 values for rTRPA1 and hTRPA1 of AM-0902, a strong and selective TRPA1 antagonist, are 71 and 131 nM, respectively. With an average Papp of 44.5 μcm/s in MDCK cells, AM-0902 is highly permeable. It also shows strong solubility (PBS pH 7.4: 226 μM, SIF: 248 μM) and is unlikely to be a substrate for P-gp (efflux ratio = 1.3 in P-gp overexpressing MDCK cells). At doses up to 10 μM, AM-0902 showed no action against rat TRPV1, TRPV3, or TRPM8, nor against human TRPV1 or TRPV4. This indicates that AM-0902 has strong selectivity over other TRP channels. With an IC50 of 0.019 μM, AM-0902 decreases 45Ca2+ flow subsequent to rat TRPA1 activation with methylglyoxal[1].
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| ln Vivo |
In vivo, AM-0902 is a strong and specific antagonist of TRPA1. Rats (t1/2=0.6 hours and 2.8 hours for rat (0.5 mg/kg, IV), rat (30 mg/kg, PO)) have a moderate terminal elimination half-life for AM-0902. AM-0902 was found to reduce allyl isothiocyanate (AITC)-induced withdrawal in a dose-dependent manner; withdrawal was significantly reduced following dosages of 10 and 30 mg/kg. For 1, 3, 10, and 30 mg/kg doses, the 1-hour unbound plasma concentrations (Cu) were 0.051±0.024 (n=8), 0.19±0.11 (n=8), 0.58±0.35 (n=8), and 2.2±0.40 (n=8) μM, respectively. These values covered the in vitro rat TRPA1 45Ca2+ IC50 by 0.72, 2.7, 8.2, and 30.3 times, respectively. This target coverage model showed good exposure-response connections. The unbound in vivo IC90 is 1.7 μM, while the unbound in vivo IC50 is 0.35 μM, which is extremely comparable with the in vitro rat TRPA1 45Ca2+ IC50. Remarkably, AM-0902's binding concentration to TRPA1 at a dose of 30 mg/kg was greater than the in vivo IC90, indicating its potential utility in investigating acute pain models in vivo [1].
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| References |
[1]. Schenkel LB, et al. Optimization of a Novel Quinazolinone-Based Series of Transient Receptor Potential A1 (TRPA1)Antagonists Demonstrating Potent in Vivo Activity. J Med Chem. 2016 Mar 24;59(6):2794-809
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| Molecular Formula |
C17H15CLN6O2
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|---|---|
| Molecular Weight |
370.793001413345
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| CAS # |
1883711-97-4
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| SMILES |
O=C1N(CC2=NC(CCC3=CC=C(Cl)C=C3)=NO2)C=NC4=C1N(C)C=N4
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| InChi Key |
AWJBWNUUODWOKQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15ClN6O2/c1-23-9-19-16-15(23)17(25)24(10-20-16)8-14-21-13(22-26-14)7-4-11-2-5-12(18)6-3-11/h2-3,5-6,9-10H,4,7-8H2,1H3
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| Chemical Name |
1-((3-(4-chlorophenethyl)-1,2,4-oxadiazol-5-yl)methyl)-7-methyl-1,7-dihydro-6H-purin-6-one
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| Synonyms |
AM-0902 AM 0902 AM0902.
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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 : ~150 mg/mL (~404.54 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.74 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 (6.74 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 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.74 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 | 2.6969 mL | 13.4847 mL | 26.9694 mL | |
| 5 mM | 0.5394 mL | 2.6969 mL | 5.3939 mL | |
| 10 mM | 0.2697 mL | 1.3485 mL | 2.6969 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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