| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
ROCK1 (Ki = 2 nM); ROCK2 (Ki = 2 nM); PKA (Ki = 69 nM); MRCKA (Ki = 28 nM); CAM2A (Ki = 5855 nM); PKC theta (Ki = 9322 nM)
Verosudil targets Rho-associated protein kinase (ROCK), specifically both ROCK1 and ROCK2 isoforms, with Ki values of 2 nM each. It also shows inhibitory activity against PKA, MRCKA, CAM2A, and PKC theta at higher concentrations. By inhibiting ROCK, Verosudil relaxes vascular smooth muscle, reduces intraocular pressure, and improves blood flow. Its primary mechanism in glaucoma involves increasing aqueous humor outflow through the trabecular meshwork. |
|---|---|
| ln Vitro |
In vitro, Verosudil is a potent ROCK inhibitor with Ki of 2 nM for both ROCK1 and ROCK2. It shows selectivity for ROCK over other kinases including PKA, MRCKA, and CAM2A. The compound's ability to inhibit ROCK activity has been demonstrated in kinase assays using recombinant enzymes. Its potency and selectivity support its use as a tool for studying ROCK-mediated cellular processes.
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| ln Vivo |
In vivo, Verosudil effectively lowers intraocular pressure primarily by increasing aqueous humor outflow through the trabecular meshwork. It has been investigated in animal models of glaucoma and ocular hypertension. A Phase II study for ocular hypertension in the USA was discontinued in June 2013. The compound's IOP-lowering effect has been demonstrated in preclinical models. Its vascular effects may also have cardiovascular applications.
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| Enzyme Assay |
In vitro enzyme assays for Verosudil use recombinant ROCK1 and ROCK2 enzymes. Kinase activity is measured using a peptide substrate and ATP, with phosphorylation quantified by methods such as radiometric (³³P-ATP) or fluorescence-based assays (e.g., Transcreener, ADP-Glo). Various concentrations of Verosudil are incubated with enzyme and substrate. Ki or IC50 values are calculated from dose-response curves. Selectivity profiling against a panel of kinases (PKA, MRCKA, CAM2A, PKC theta) is performed.
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| Cell Assay |
Cellular assays for Verosudil utilize cell lines such as trabecular meshwork cells or vascular smooth muscle cells. Cells are treated with various concentrations of Verosudil. ROCK activity is assessed by measuring phosphorylation of downstream targets such as myosin light chain (MLC) or cofilin by Western blotting. Cell morphology (e.g., stress fiber formation) and cell migration are assessed to confirm ROCK inhibition. These assays confirm functional activity.
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| Animal Protocol |
In vivo animal studies for Verosudil utilize models of ocular hypertension, such as laser-induced or steroid-induced ocular hypertension models in rabbits or monkeys. The compound is administered as eye drops at various concentrations. Intraocular pressure is measured using tonometry at multiple time points post-administration. Aqueous humor outflow facility is assessed by tonography. Efficacy is compared to vehicle and reference IOP-lowering agents (e.g., latanoprost, timolol).
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| ADME/Pharmacokinetics |
Verosudil is designed for topical ocular administration as eye drops. As a small molecule with molecular weight of 327.4 g/mol (C₁₇H₁₇N₃O₂S), it has suitable properties for ocular delivery. The compound's pharmacokinetic profile in the eye (corneal penetration, aqueous humor concentration, duration of action) is important for its IOP-lowering effect. Systemic absorption is minimal with topical administration. Detailed PK parameters would be determined in ocular pharmacokinetic studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity of Verosudil has been evaluated in standard toxicology studies to support ophthalmic development. As a ROCK inhibitor, potential ocular adverse effects may include conjunctival hyperemia, corneal effects, and inflammation. Systemic effects are expected to be minimal with topical administration. The Phase II discontinuation may have been due to efficacy, safety, or strategic reasons. The compound's safety profile supports further investigation.
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| References |
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| Additional Infomation |
Verosudil (AR-12286, AR-11324) is a potent, selective ROCK inhibitor with Ki of 2 nM for ROCK1 and ROCK2. It lowers IOP by increasing aqueous humor outflow. It was investigated for glaucoma and ocular hypertension. A Phase II study for ocular hypertension was discontinued. It is available for research purposes only.
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| Molecular Formula |
C17H17N3O2S
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|---|---|
| Molecular Weight |
327.4
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| Exact Mass |
327.104
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| Elemental Analysis |
C, 62.37; H, 5.23; N, 12.83; O, 9.77; S, 9.79
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| CAS # |
1414854-42-4
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| Related CAS # |
1414854-42-4;1414854-44-6 (HCl);
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| PubChem CID |
66906051
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| Appearance |
White to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
625.5±55.0 °C at 760 mmHg
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| Flash Point |
332.1±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.666
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| LogP |
0.84
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
494
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)C(C1=CSC=C1)C(=O)NC2=CC=C3C(=C2)C=CNC3=O
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| InChi Key |
VDYRZXYYQMMFJW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H17N3O2S/c1-20(2)15(12-6-8-23-10-12)17(22)19-13-3-4-14-11(9-13)5-7-18-16(14)21/h3-10,15H,1-2H3,(H,18,21)(H,19,22)
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| Chemical Name |
2-(dimethylamino)-N-(1-oxo-2H-isoquinolin-6-yl)-2-thiophen-3-ylacetamide
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| Synonyms |
Verosudil free base; AR12286; AR-12286; AR 12286; Verosudil
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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: ~16.7 mg/mL (~50.9 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (5.10 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 16.7 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: ≥ 1.67 mg/mL (5.10 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 16.7 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: ≥ 1.67 mg/mL (5.10 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 | 3.0544 mL | 15.2718 mL | 30.5437 mL | |
| 5 mM | 0.6109 mL | 3.0544 mL | 6.1087 mL | |
| 10 mM | 0.3054 mL | 1.5272 mL | 3.0544 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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