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| 25mg |
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Purity: ≥98%
SR-3677 (SR3677) is a potent and selective Rho-kinase/ROCK2 inhibitor with anticancer activity. In enzyme-based assays for ROCK-II and ROCK-I, it inhibits ROCK with IC50 values of 3 and 56 nM, respectively. With respect to 353 kinases, SR-3677's off-target hit rate was 1.4%, and it only inhibited three of the seventy nonkinase enzymes and receptors. Pharmacological investigations demonstrated the effectiveness of SR-3677 in both cases, enhancing the outflow of aqueous humor in vivo in the eyes of pigs and preventing the phosphorylation of the myosin light chain.
| Targets |
ROCK-II (IC50 = 3 nM); ROCK-I (IC50 = 56 nM)
SR-3677 (compound 5) is a potent and highly selective inhibitor of Rho kinase II (ROCK-II), with an IC50 of approximately 3 nM in enzyme and cell-based assays [1] |
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| ln Vitro |
SR-3677 has an off-target hit rate of 1.4% against 353 kinases, an IC50 of approximately 3 nM in enzyme and cell-based assays, and only 3 out of 70 nonkinase enzymes and receptors that it inhibits. For ROCK-I, SR-3677's IC50 value is 56±12 nM. The primary cause of SR-3677's high potency is the hydrophobic interaction between the benzodioxane phenyl ring and the hydrophobic pocket surface. 1. SR-3677 exhibited high selectivity in kinase profiling: it had an off-target hit rate of only 1.4% against a panel of 353 kinases, meaning it showed inhibitory activity against very few other kinases besides ROCK-II [1] 2. In non-kinase enzyme and receptor screening, SR-3677 inhibited only 3 out of 70 tested non-kinase enzymes and receptors, further demonstrating its high selectivity [1] 3. SR-3677 inhibited myosin light chain phosphorylation in in vitro/cell-based systems[1] |
| ln Vivo |
SR-3677 is effective in both, as demonstrated by pharmacology studies, which also show that it inhibits myosin light chain phosphorylation and increases ex vivo aqueous humor outflow in in pig eyes. The outflow facility is increased by 60% at one hour of perfusion with continuous exposure to 25 µM SR-3677, and by 70–80% at two to five hours.
1. Ex vivo experiments using enucleated porcine eyes showed that perfusion with 25 µM SR-3677 significantly increased aqueous humor outflow facility (N = 3; average ± SE; p < 0.05; p < 0.01), indicating efficacy in modulating ocular outflow function [1] |
| Enzyme Assay |
The STK2 kinase system from Cisbio is used for assays. The wells are filled with a 5 μL mixture of ATP (ROCK-I: 4 μM; ROCK-II: 20 μM) and a 1 μM STK2 substrate in STK-buffer. Test compounds (SR-3677) are dispensed in 20 nL. To initiate the reaction, add 5 μL of either 0.5 nM ROCK-II or 2.5 nM ROCK-I in STK-buffer. Addition of 10 μL of 1x antibody and 62.5 nM Sa-XL in detection buffer stops the reaction after 4 hours at room temperature[1].
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| Animal Protocol |
NA
ExVivo 1. Ex vivo porcine eye experiment: Enucleated porcine eyes were used, and 25 µM SR-3677 was perfused into the eyes to evaluate aqueous humor outflow facility. The experiment included 3 replicates, and data were presented as average ± standard error (SE), with statistical significance determined (p < 0.05 and p < 0.01). No information on drug dissolution formula, frequency of perfusion, or long-term administration was provided [1] |
| References | |
| Additional Infomation |
1. SR-3677 belongs to a new class of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides, which are designed as potent and highly selective ROCK-II inhibitors [1]
2. The molecular structure of SR-3677 was docked into the catalytic domain of a ROCK-II homology model (structural interaction details not elaborated) [1] 3. A synthetic route for SR-3677 (compound 5) was provided: (a) Reaction with NaH in THF with 2-(dimethylamino)ethanol at room temperature (yield 92%); (b) Reduction with SnCl₂ in ethanol at 70 °C (yield 91%); (c) Coupling with benzodioxane-2-carboxylic acid using HATU/DIEA in DMF at room temperature (yield 75%); (d) Cross-coupling with 4-1H-pyrazoleboronic acid pinacol ester using Pd[P(Ph)₃]₄ and K₂CO₃ in dioxane/H₂O at 95 °C (yield 35%) [1] 4. ROCK inhibitors (including SR-3677) have potential therapeutic relevance for neurological disorders, cardiovascular diseases (e.g., coronary artery spasm), and ocular conditions (e.g., modulating aqueous humor outflow), [1] |
| Molecular Formula |
C22H24N4O4
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|---|---|---|
| Molecular Weight |
408.45
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| Exact Mass |
408.179
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| Elemental Analysis |
C, 64.69; H, 5.92; N, 13.72; O, 15.67
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| CAS # |
1072959-67-1
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| Related CAS # |
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| PubChem CID |
25093235
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| Appearance |
White to off-white solid
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
646.9±55.0 °C at 760 mmHg
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| Flash Point |
345.0±31.5 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.632
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| LogP |
2.34
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
563
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)CCOC1=C(NC(C2OC(C=CC=C3)=C3OC2)=O)C=CC(C4=CNN=C4)=C1
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| InChi Key |
OQWZIAVXCYIZNN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24N4O4/c1-26(2)9-10-28-20-11-15(16-12-23-24-13-16)7-8-17(20)25-22(27)21-14-29-18-5-3-4-6-19(18)30-21/h3-8,11-13,21H,9-10,14H2,1-2H3,(H,23,24)(H,25,27)
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| Chemical Name |
N-[2-[2-(dimethylamino)ethoxy]-4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-1,4-benzodioxine-3-carboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.03.00
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.12 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 (6.12 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (6.12 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 | 2.4483 mL | 12.2414 mL | 24.4828 mL | |
| 5 mM | 0.4897 mL | 2.4483 mL | 4.8966 mL | |
| 10 mM | 0.2448 mL | 1.2241 mL | 2.4483 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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