| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
ROCK; norepinephrine transporter (NET)
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| ln Vivo |
Six hours after a single dose of 0.04% AR-13324 to 7 normal monkey eyes, C was increased (P<0.05) by 53% in drug-treated eyes compared with either contralateral vehicle-treated control eyes or baseline measurements. The IOP measured by pneumatonometer in treated eyes was reduced (P<0.005) by 25% when compared with baseline measurements and by 24% when compared with contralateral vehicle-treated eyes. For 6 hours after a single dose of 0.04% AR-13324, F was reduced (P<0.05) by 20% and 23% when compared with contralateral vehicle-treated eyes and baseline values, respectively.
Conclusions: AR-13324 reduces IOP in normotensive monkey eyes. A dual mechanism of action, increase in tonographic outflow facility, and decrease of aqueous humor flow rates, accounts for the IOP reduction in normotensive monkey eyes.[1]
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| Animal Protocol |
Seven normotensive monkeys were used. Tonographic outflow facility (C) was measured before drug administration and repeated 6 hours after administration of 50 µL (25 µL×2) of 0.04% AR-13324 to 1 eye and an equal volume of vehicle to the contralateral control eye. Baseline aqueous humor flow rates (F) were measured hourly for 6 hours beginning at 10:00 AM on day 1. On day 2, 50 µL (25 µL×2) of 0.04% AR-13324 was applied to 1 eye of each animal and vehicle to the fellow eye at 8:00 AM. Aqueous humor flow rates were measured at the same times as on the baseline day beginning 2 hours after dosing.[1]
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| References |
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| Additional Infomation |
Purpose: To evaluate the ocular and systemic safety and systemic absorption of AR-13324 in normotensive, healthy volunteers.
Design: Open-label, noncomparative, single-arm phase 1 clinical trial. Methods: setting: Phase 1 clinical trials unit. patient or study population: Eighteen normal adult volunteers. intervention or observation procedures: Subjects received AR-13324 ophthalmic solution 0.02% once daily in the morning in each eye for 8 days. Main outcome measures: Plasma concentrations of AR-13324 and its presumed human metabolite, AR-13503, and ocular safety measures. Results: There were no observed plasma AR-13324 concentrations higher than the lower limit of quantitation at any time point in any subject. Only 1 plasma sample from 1 subject (day 8 at 8 hours after dose administration) had an AR-13503 concentration higher than the lower limit of quantitation (0.11 ng/mL). AR-13324 dosed once daily in the morning produced substantial reductions in baseline intraocular pressure of up to 6 mm Hg that were statistically significant (P < .001) at all time points after dose administration. All but 1 subject exhibited transient conjunctival hyperemia to some degree in the 8-hour period after morning dosing. Conclusions: AR-13324 ophthalmic solution 0.2%, administered once daily in the morning for 8 days, produced little or no quantifiable systemic exposure to the parent compound or a presumed metabolite. Clinically and statistically significant reductions in intraocular pressure were observed in these normotensive subjects that were more pronounced compared with what has been observed commonly with other ocular hypotensive therapies in this population.[2] |
| Molecular Formula |
C29H33N3O9S2
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|---|---|
| Molecular Weight |
631.72
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| Exact Mass |
535.1777
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| CAS # |
2095432-73-6
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| Related CAS # |
Netarsudil dimesylate;1422144-42-0;Netarsudil hydrochloride;1253952-02-1
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| PubChem CID |
171921137
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| Appearance |
Light brown to brown Liquid
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| InChi Key |
MPAAEFZQVJRGLO-VQIWEWKSSA-N
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| InChi Code |
InChI=1S/C27H25N3O3.CH4O3S/c1-17-3-10-24(18(2)13-17)27(32)33-23-8-5-19(6-9-23)25(15-28)26(31)30-22-7-4-21-16-29-12-11-20(21)14-22;1-5(2,3)4/h3-14,16,25H,15,28H2,1-2H3,(H,30,31);1H3,(H,2,3,4)/t25-;/m1./s1
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| Chemical Name |
[4-[(2S)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl] 2,4-dimethylbenzoate;methanesulfonic acid
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| Synonyms |
2095432-73-6; Benzoic acid, 2,4-dimethyl-, 4-[(1S)-1-(aminomethyl)-2-(6-isoquinolinylamino)-2-oxoethyl]phenyl ester, compd. with methanesulfonate (1:2)
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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 :≥ 28 mg/mL (~44.32 mM)
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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 | 1.5830 mL | 7.9149 mL | 15.8298 mL | |
| 5 mM | 0.3166 mL | 1.5830 mL | 3.1660 mL | |
| 10 mM | 0.1583 mL | 0.7915 mL | 1.5830 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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