AR-13324 mesylate
(Synonyms: 奈他地尔二甲磺酸盐) 目录号 : GC19034
AR-13324 是一种有效的 ROCK I 和 ROCK II 抑制剂，已被证明可在低浓度下诱导培养的人和猪 TM 细胞发生形态学变化。
Cas No.:1422144-42-0
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
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.
AR-13324 是一种有效的 ROCK I 和 ROCK II 抑制剂,已被证明可在低浓度下诱导培养的人和猪 TM 细胞发生形态学变化。 AR-13324 是一种 rho 激酶抑制剂和去甲肾上腺素转运蛋白抑制剂,可降低血压正常的猴眼的眼内压 (IOP)[1]。 AR-13324 在 DB 兔 [2] 中产生具有统计学意义的 EVP 降低。
PG324 眼用溶液中 AR-13324 0.02% 和拉坦前列素 0.005% 的固定剂量组合在相同浓度下提供了临床和统计学上优于其单个活性成分的降眼压效果[3] . AR-13324 0.02% 比拉坦前列素低约 1 毫米汞柱,用于非药物眼压在 22 至 35 毫米汞柱范围内的患者 [4]
向 7 只正常猴眼单次给药 0.04% AR-13324 后 6 小时,与基线测量值相比,治疗眼中通过气压计测量的 IOP 降低 (P< 0.005) 25%,与基线测量值相比降低 24%对侧经载体处理的眼睛 [1]。给药后 3 小时,AR-13324 治疗引起的 EVP 降低占测得 IOP 降低的 42%[2]。
| 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. |
|
| Cas No. | 1422144-42-0 | SDF | |
| 别名 | 奈他地尔二甲磺酸盐 | ||
| 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 | ||
| 分子式 | C30H35N3O9S2 | 分子量 | 645.74 |
| 溶解度 | DMSO : 100 mg/mL (154.86 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.5486 mL | 7.7431 mL | 15.4861 mL |
| 5 mM | 0.3097 mL | 1.5486 mL | 3.0972 mL |
| 10 mM | 0.1549 mL | 0.7743 mL | 1.5486 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet