Verosudil (AR-11324; AR 11324; AR11324) is a novel and potent Rho kinase inhibitor with anti-hypertensive activity. It inhibits ROCK1 and ROCK2 at 2 and 2 nM Kis, respectively. Glaucoma treatment is one possible application for it.
Physicochemical Properties
| Molecular Formula | C17H17N3O2S |
| Molecular Weight | 327.4 |
| Exact Mass | 327.104 |
| Elemental Analysis | C, 62.37; H, 5.23; N, 12.83; O, 9.77; S, 9.79 |
| CAS # | 1414854-42-4 |
| Related CAS # | 1414854-42-4;1414854-44-6 (HCl); |
| PubChem CID | 66906051 |
| Appearance | White to light yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 625.5±55.0 °C at 760 mmHg |
| Flash Point | 332.1±31.5 °C |
| Vapour Pressure | 0.0±1.8 mmHg at 25°C |
| Index of Refraction | 1.666 |
| LogP | 0.84 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 23 |
| Complexity | 494 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CN(C)C(C1=CSC=C1)C(=O)NC2=CC=C3C(=C2)C=CNC3=O |
| InChi Key | VDYRZXYYQMMFJW-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 2-(dimethylamino)-N-(1-oxo-2H-isoquinolin-6-yl)-2-thiophen-3-ylacetamide |
| Synonyms | Verosudil free base; AR12286; AR-12286; AR 12286; Verosudil |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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) |
| References |
[1]. Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma. J Ocul Pharmacol Ther. 2018;34(1-2):40‐51 [2]. Ocular hypotensive efficacy, safety and systemic absorption of AR-12286 ophthalmic solution in normal volunteers. Br J Ophthalmol. 2013;97(5):567‐572. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~16.7 mg/mL (~50.9 mM) |
| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |