| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
ROCK/PKC; metabolite of Netarsudil
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|---|---|
| ln Vitro |
Human venous vascular endothelial cell (HUVEC) tube formation is inhibited by AR-13503 (16 hours) at an IC50 of 21 nM[1]. In a dose-dependent approach, AR-13503 (400 nM; 5 days) decreases the sprouting area of venous vasculature [1]. In a dose-dependent manner, AR-13503 (400 nM; 2 weeks) improves the primary RPE barrier function in pigs [1].
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| ln Vivo |
In combination with Aflibercept, AR-13503 (1.25 mg/kg; intraperitoneal injection; once daily for 5 days) effectively inhibits the development of aberrant neovascularization (NV) [1].
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| Animal Protocol |
Animal/Disease Models: Oxygen-induced retinopathy (OIR) mouse model (C57BL/6; 7 days old) [1]
Doses: 1.25 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 5 days Experimental Results: Combination treatment group The reduction in NV (approximately 75%) was greater than that in the aflibercept alone group (approximately 55%). In the oxygen-induced retinopathy (OIR) animal model, 7-day old neonatal C57BL/6 mice were housed with foster mothers at 75% oxygen from postnatal day (P)7 to P12. Upon return to normoxia on P12, mice were treated by once daily intraperitoneal injections with vehicle control, aflibercept, or AR-13503 in combination with aflibercept. Tissues were harvested following 5 days of treatment and stained for isolectin-IB4 for visualization and analysis of NV. Retinas were also harvested for pharmacokinetic analysis.[2] |
| References |
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| Additional Infomation |
Diabetic retinopathy (DR) and its complications can lead to irreversible vision loss. Due to the limitations of anti-vascular endothelial growth factor (VEGF) and steroid therapy, there is an urgent need for new therapies with novel mechanisms of action. Rho kinase (ROCK) is closely associated with retinal neovascularization (NV) and vascular leakage in neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR). AR-13503 is a potent ROCK and protein kinase C (PKC) inhibitor. We have demonstrated in vitro and in vitro experiments that AR-13503 can inhibit angiogenesis and enhance the function of the retinal pigment epithelium barrier. This study investigated the effect of AR-13503 on abnormal neovascularization (NV) formation in an animal model of proliferative diabetic retinopathy (PDR). [2] Results: AR-13503 was detectable in the retina of mice after systemic administration of 1.25 mg/kg/day. Compared with the vector control group, mice treated with aflibercept alone had approximately 55% less NV. AR-13503 combined with aflibercept resulted in a greater reduction in NV (approximately 75%), which was superior to aflibercept alone. There was no significant difference in avascular area among the groups. [2]
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| Molecular Formula |
C19H19N3O2
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|---|---|
| Exact Mass |
321.147
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| Elemental Analysis |
C, 71.01; H, 5.96; N, 13.08; O, 9.96
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| CAS # |
1254032-16-0
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| Related CAS # |
1422144-42-0 (mesylate);1254032-66-0;1253952-02-1 (HCl);1254032-16-0;
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| PubChem CID |
134128281
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| Appearance |
White to off-white solid powder
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
409
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C([C@H](CN)C1C=CC(CO)=CC=1)NC1C=CC2C=NC=CC=2C=1
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| InChi Key |
LTXBFJFJUIJOQE-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C19H19N3O2/c20-10-18(14-3-1-13(12-23)2-4-14)19(24)22-17-6-5-16-11-21-8-7-15(16)9-17/h1-9,11,18,23H,10,12,20H2,(H,22,24)/t18-/m1/s1
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| Chemical Name |
(2S)-3-amino-2-[4-(hydroxymethyl)phenyl]-N-isoquinolin-6-ylpropanamide
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| Synonyms |
AR-11324 metabolite; AR13503; AR11324 metabolite; AR-13324 M1 metabolite; AR-13503; 2309668-15-1; 4MVW7F3BCT; Netarsudil metabolite AR-13503; UNII-4MVW7F3BCT; 1254032-16-0; CHEMBL4753043; Netarsudil metabolite; AR 11324 metabolite; AR-13503 AR 13503
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
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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