| 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 |
Purity: =99.04%
| Targets |
ROCK-I 3.7 nM (IC50) ROCK-II 2.3 nM (IC50)
Sovesudil targets Rho-associated protein kinase (ROCK), specifically ROCK I and ROCK II. It is an ATP-competitive inhibitor, meaning it competes with ATP for binding to the kinase. By inhibiting ROCK, it modulates the actin cytoskeleton and cellular contractility, leading to a reduction in intraocular pressure. ROCK is a validated target for glaucoma therapy. |
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| ln Vitro |
In human trabecular meshwork (HTM) cells, sovesudil (PHP-201) (1 μM; 60 minutes) causes alterations in cellular activity [1].
In vitro, sovesudil (PHP-201) (1 μM; 60 minutes) causes alterations in cellular activity in human trabecular meshwork (HTM) cells. It is a potent inhibitor of ROCK I and ROCK II with IC50 values of 3.7 and 2.3 nM, respectively. These activities have been demonstrated in biochemical and cell-based assays. |
| ln Vivo |
In both normotensive and acutely hypertensive rabbits, sovesudil (0.1%, 0.3%, and 0.5%; male New Zealand white rabbits) efficiently lowers intraocular pressure (IOP) without producing noticeably high levels of hyperemia [1].
In vivo, Sovesudil reduces intraocular pressure without causing hyperemia. This effect is consistent with its mechanism of action as a ROCK inhibitor and its local administration. The compound has been investigated for the treatment of glaucoma and ocular hypertension. |
| Enzyme Assay |
The in vitro kinase assay for Sovesudil involves measuring its inhibitory activity against ROCK I and ROCK II. This is a biochemical assay using recombinant ROCK kinases. The compound's IC50 values of 3.7 and 2.3 nM are determined from these assays. The ATP-competitive nature of the inhibition is confirmed by measuring its activity at different ATP concentrations.
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| Cell Assay |
Cellular assays for Sovesudil are performed using human trabecular meshwork (HTM) cells. Cells are treated with the compound, and its effects on cellular activity, such as actin cytoskeleton organization and cell contractility, are assessed. These assays confirm its activity in a cellular context.
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| Animal Protocol |
In vivo animal protocols for Sovesudil involve administering the compound locally to animal models of ocular hypertension. Intraocular pressure is measured to assess the compound's efficacy. The absence of hyperemia is also noted as a favorable safety feature. These studies provide preclinical evidence for its potential in treating glaucoma.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of Sovesudil are consistent with its local administration. As a locally acting ROCK inhibitor, it is designed to have a favorable ocular PK profile. The compound is typically administered topically. Its systemic exposure is expected to be low, minimizing systemic side effects.
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| Toxicity/Toxicokinetics |
Toxicity data for Sovesudil are limited. As a locally acting ROCK inhibitor, it is expected to have a favorable safety profile, with minimal systemic toxicity. The compound has been investigated in clinical trials. Comprehensive toxicological data are available from these studies, but not detailed here.
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| References |
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| Additional Infomation |
Sovesudil (PHP-201; AMA0076) is a potent ROCK inhibitor that reduces intraocular pressure. It has been investigated for the treatment of glaucoma. The compound is not currently approved for clinical use and is intended for research purposes.
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| Molecular Formula |
C23H22FN3O3
|
|---|---|
| Molecular Weight |
407.437489032745
|
| Exact Mass |
407.164
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| CAS # |
1333400-14-8
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| Related CAS # |
Sovesudil hydrochloride
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| PubChem CID |
68245749
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
545.9±50.0 °C at 760 mmHg
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| Flash Point |
284.0±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.619
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| LogP |
3.73
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
30
|
| Complexity |
576
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1(C2=CC(C(NC3C=CN=CC=3F)=O)=CC=C2CN)=CC=CC(C(OCCC)=O)=C1
|
| InChi Key |
PNWBYIFLWUCWKS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H22FN3O3/c1-2-10-30-23(29)17-5-3-4-15(11-17)19-12-16(6-7-18(19)13-25)22(28)27-21-8-9-26-14-20(21)24/h3-9,11-12,14H,2,10,13,25H2,1H3,(H,26,27,28)
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| Chemical Name |
propyl 3-[2-(aminomethyl)-5-[(3-fluoropyridin-4-yl)carbamoyl]phenyl]benzoate
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| Synonyms |
Sovesudil; 1333400-14-8; PHP-201; PHP201; AMA 0076; AMA-0076; Ama0076;
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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 : 100 mg/mL (245.43 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.14 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 25.0 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: ≥ 2.5 mg/mL (6.14 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 25.0 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: ≥ 2.5 mg/mL (6.14 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 | 2.4543 mL | 12.2717 mL | 24.5435 mL | |
| 5 mM | 0.4909 mL | 2.4543 mL | 4.9087 mL | |
| 10 mM | 0.2454 mL | 1.2272 mL | 2.4543 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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