| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
ROCK-I 3.7 nM (IC50) ROCK-II 2.3 nM (IC50)
Rho-associated protein kinase (ROCK), specifically ROCK-I and ROCK-II. Sovesudil hydrochloride competitively binds to the ATP-binding pocket of ROCK, with IC50 values of 3.7 nM for ROCK-I and 2.3 nM for ROCK-II. Its inhibition initiates a cascade of dephosphorylation events, primarily affecting the Myosin Light Chain Phosphatase and the LIM Kinase/Cofilin axes, leading to cytoskeletal relaxation. |
|---|---|
| ln Vitro |
Human trabecular meshwork (HTM) cells can exhibit changed cellular behavior when exposed to sovesudil(PHP-201)(1 μM; 60 min) hydrochloride[1].
In vitro, Sovesudil hydrochloride potently and selectively inhibits ROCK activity. This inhibition leads to the relaxation of pre-contracted trabecular meshwork (TM) cells and reduces contraction of the ciliary muscle. These effects increase the conventional (trabecular) and uveoscleral outflow pathways of aqueous humor, effectively lowering IOP. Its high selectivity for ROCK minimizes off-target kinase interactions. |
| ln Vivo |
In ocular normotensive and acute hypertensive rabbits, sovesudil hydrochloride (0.1%, 0.3%, and 0.5%; male New Zealand White rabbits) significantly lowers Intraocular Pressure (IOP) without producing pronounced hyperemia[1].
In vivo, Sovesudil hydrochloride effectively reduces intraocular pressure (IOP) in preclinical models. In New Zealand White rabbits, topical ocular administration of the compound leads to a significant, dose-dependent reduction in IOP with a rapid onset of action. A key finding is that this IOP reduction is not accompanied by conjunctival hyperemia, a common side effect associated with earlier ROCK inhibitors, suggesting a differentiated clinical profile. |
| Enzyme Assay |
A non-cellular, recombinant ROCK enzyme assay is performed. ROCK-I or ROCK-II protein is incubated with a fluorescently-labeled peptide substrate (e.g., FAM-S6K peptide) and increasing concentrations of Sovesudil hydrochloride (0-100 nM) in the presence of ATP. After a 60-minute incubation, the reaction is stopped. The ratio of phosphorylated to unphosphorylated substrate is measured by fluorescence polarization or capillary electrophoresis, and the IC50 is calculated.
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| Cell Assay |
Primary human trabecular meshwork (HTM) cells are cultured in 96-well plates and serum-starved overnight. Cells are treated with Sovesudil hydrochloride (0.1-1000 nM) for 1 hour. To measure the functional effect, cells are then stimulated with lysophosphatidic acid (LPA) to induce actin stress fiber formation. Cells are fixed and stained with phalloidin (F-actin) and p-MLC antibody. The loss of actin stress fibers and p-MLC is quantified by high-content imaging.
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| Animal Protocol |
Normotensive or ocular hypertensive New Zealand White rabbits are used. After baseline IOP measurement, a single 50 microL drop of Sovesudil hydrochloride (0.1%-1%) is administered topically to one eye, while the contralateral eye receives vehicle. IOP is then measured at multiple time points (e.g., 0.5, 1, 2, 4, 6, 8, 24 h) post-dose. Conjunctival hyperemia is scored visually or with a slit lamp. The percent reduction in IOP and the time to peak effect are calculated.
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| ADME/Pharmacokinetics |
As a topically administered ocular compound, Sovesudil hydrochloride is designed for local delivery. In rabbits, peak IOP reduction occurs within 1-2 hours post-dose, and effects can persist for up to 6-8 hours. Systemic exposure is minimal with topical administration, limiting potential systemic side effects. The compound has a molecular weight of 443.90 (hydrochloride salt).
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| Toxicity/Toxicokinetics |
Sovesudil hydrochloride is a research compound and has not been approved for human use. In preclinical ocular safety studies, it is well-tolerated. The primary differentiator is the lack of hyperemia, indicating a lower risk of vascular side effects. High concentrations may cause transient stinging upon instillation, but no significant corneal or retinal toxicities have been reported. Standard laboratory safety precautions should be followed.
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| References |
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| Additional Infomation |
Sovesudil (PHP-201, AMA0076) hydrochloride is a highly selective ROCK inhibitor that advanced into clinical development for glaucoma. Clinical trials have confirmed its IOP-lowering efficacy and favorable tolerability with minimal hyperemia. The compound is now available as a research-grade molecule for non-clinical studies. It is for research use only and should be stored as a powder at -20degC, protected from light and moisture.
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| Molecular Formula |
C23H23CLFN3O3
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|---|---|
| Molecular Weight |
443.9
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| CAS # |
2984963-50-8
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| Related CAS # |
Sovesudil;1333400-14-8
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| Appearance |
Light brown to brown solid powder
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 :~62.5 mg/mL (~140.80 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.69 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2528 mL | 11.2638 mL | 22.5276 mL | |
| 5 mM | 0.4506 mL | 2.2528 mL | 4.5055 mL | |
| 10 mM | 0.2253 mL | 1.1264 mL | 2.2528 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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