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AR-13324 mesylate

Catalog No.GC19034

AR-13324 mesylate Chemical Structure

AR-13324 is a potent inhibitor of ROCK I and ROCK II that has been shown to induce morphologic changes in cultured human and porcine TM cells at low concentration.

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2mg
$122.00
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5mg
$244.00
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10mg
$435.00
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50mg
$1,654.00
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100mg
$2,524.00
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Sample solution is provided at 25 µL, 10mM.

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Protocol

Animal experiment [1]:

Animal models

Seven adult female cynomolgus monkeys, each weighing 3 to 5 kg with normotensive IOP

Preparation Method

50 μL (25 μL×2) of 0.04% AR-13324 was topically applied to 1 eye of each monkey. An equal volume of vehicle was applied to the contralateral control eye. IOP was measured before drug administration and 6 hours after dosing with a calibrated neumatonometer in the sit ting position. IOP reading was taken 2 times on each eye and the average of 2 values was used to perform statistical analysis.

Dosage form

50 μL (25 μL×2) of 0.04% AR-13324

Applications

Six hours after a single dose of 0.04% AR-13324 to 7 normal monkey eyes, 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

Animal experiment [2]:

Animal models

Male DB rabbits (n=11, 2.15-0.09 kg)

Preparation Method

The protocol entailed once per day—topical application of 1 drop of 0.04% AR-13324 for 2 days. Then, on the morning of the third day,the animals were anesthetized and surgically prepared, and then, measurements were obtained before dosing with AR-13324 or vehicle (baseline measurements) and for 3 h after dosing.

Dosage form

1 drop of 0.04% AR-13324 for 2 days

Applications

At 3 h postdosing, the reduction in EVP caused by AR-13324 treatment accounted for 42% of the measured reduction in IOP.

References:

[1]. Wang RF, et al. Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma. 2015 Jan;24(1):51-4.

[2]. Kiel JW, Kopczynski CC. Effect of AR-13324 on episcleral venous pressure in Dutch belted rabbits. J Ocul Pharmacol Ther. 2015 Apr;31(3):146-51.

Background

AR-13324 is a potent inhibitor of ROCK I and ROCK II that has been shown to induce morphologic changes in cultured human and porcine TM cells at low concentration. AR-13324, a rho kinase inhibitor, and an inhibitor of the norepinephrine transporter, reduces intraocular pressure (IOP) in normotensive monkey eyes [1]. AR-13324 produces statistically significant lowering of EVP in DB rabbits [2].

The fixed-dose combination of AR-13324 0.02% and latanoprost 0.005% in PG324 Ophthalmic Solution provides clinically and statistically superior ocular hypotensive efficacy relative to its individual active components at the same concentrations [3]. AR-13324 0.02% was less effective than latanoprost by approximately 1 mmHg in patients with unmedicated IOPs in the range of 22 to 35 mmHg [4]

Six hours after a single dose of 0.04% AR-13324 to 7 normal monkey eyes, 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 [1]. At 3 h postdosing, the reduction in EVP caused by AR-13324 treatment accounted for 42% of the measured reduction in IOP [2].

References:
[1].Wang RF, et al. Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma. 2015 Jan;24(1):51-4.
[2].Kiel JW, Kopczynski CC. Effect of AR-13324 on episcleral venous pressure in Dutch belted rabbits. J Ocul Pharmacol Ther. 2015 Apr;31(3):146-51.
[3].Lewis RA, Levy B, Ramirez N, et alFixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomised, controlled study in patients with open-angle glaucoma or ocular hypertensionBritish Journal of Ophthalmology 2016;100:339-344.
[4].Bacharach J, Dubiner HB, Levy B, Kopczynski CC, Novack GD; AR-13324-CS202 Study Group. Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure. Ophthalmology. 2015 Feb;122(2):302-7.

Chemical Properties

Cas No. 1422144-42-0 SDF
Synonyms N/A
Chemical Name N/A
Canonical SMILES CC1=CC(C)=C(C(OCC2=CC=C([C@@H](CN)C(NC3=CC(C=CN=C4)=C4C=C3)=O)C=C2)=O)C=C1.CS(=O)(O)=O.CS(=O)(O)=O
Formula C30H35N3O9S2 M.Wt 645.74
Solubility Soluble in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

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Research Update

Effect of AR-13324 on episcleral venous pressure in Dutch belted rabbits

J Ocul Pharmacol Ther2015 Apr;31(3):146-51.PMID: 25756366DOI: 10.1089/jop.2014.0146

Purpose: AR-13324 is a potential new drug for the treatment of patients with glaucoma that has been shown to lower intraocular pressure (IOP) by increasing trabecular outflow facility and decreasing aqueous production. The present study tested the hypothesis that AR-13324 also lowers IOP by reducing episcleral venous pressure (EVP).
Methods: In Dutch Belted (DB) rabbits (n=11), arterial pressure (AP), IOP, carotid blood flow (BFcar), heart rate (HR), and EVP were measured invasively. Animals were dosed with AR-13324 (0.04%, topical, n=6) once daily for 3 days. On day 3, the animals were anesthetized, and then, measurements were obtained before dosing with AR-13324 or vehicle (n=5) and for 3 h after dosing. The data (mean±standard error of the mean) were analyzed by repeated measures ANOVA with post hoc testing. Retrospective baseline data from prior similar studies in New Zealand White rabbits were also compiled.
Results: Baseline values were as follows: AP, 101±3 mmHg; IOP; 33±3 mmHg; EVP, 16±1 mmHg; BFcar, 41±4 mL/min; and HR, 330±6 bpm. Three hours after AR-13324 dosing, IOP was reduced by 39%±7% (P<0.001) and EVP decreased by 35%±4% (P<0.05); after vehicle dosing, IOP was reduced by 24%±4% (P<0.05) and EVP increased by 25%±5% (P<0.05). AP, BFcar, and HR were unchanged.
Conclusions: AR-13324 produces statistically significant lowering of EVP in DB rabbits. In addition, the baseline values for AP, IOP, EVP, BFcar, and HR in the DB rabbit are higher than those previously reported in the New Zealand rabbit.

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