| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
ROCK-2 (IC50 = 135 nM; Ki = 36 nM for human, 41 nM for rat)
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| ln Vitro |
Dapoxetine decreases the uptake of 5-HT, norepinephrine, and dopamine via binding to the transporters of these chemicals. Potency is arranged as follows: 5-HT > norepinephrine ≫ dopamine. In addition to inhibiting the uptake of [3H] norepinephrine by the norepinephrine reuptake transporter, which has an IC50 value of 1.12 nM, dapoxetine also inhibits the uptake of [3H] dopamine by the dopamine reuptake transporter, which has an IC50 value of 202 nM and 1720 nM, respectively, and [3H] 5HT by the 5-HT reuptake transporter. [1]
SAR407899 is a potent, ATP-competitive Rho kinase inhibitor. It shows an IC50 of 135 nM for ROCK-2 and Kis of 36 nM and 41 nM for human and rat ROCK-2, respectively. SAR407899 is highly selective over 117 receptor and enzyme targets. The activity of SAR407899 is approximately 8-fold greater than that of fasudil. In enzyme activity assays, 10 μM SAR407899 inhibited a few other kinases including MSK-1 (79% inhibition), PKCδ (66%), PKB (63%), and RSK (59%). In cellular assays, the compound inhibits ROCK-mediated signaling pathways and modulates vascular function. |
| ln Vivo |
In the thoracic aorta of spontaneously hypertensive rats (SHR), SAR407899 (3 mg/kg, i.v.) inhibits ROCK-mediated MYPTT696 phosphorylation. The intravenous administration of SAR407899 (0.01-0.30 mg/kg) effectively decreases the pressor response to vasoconstrictors in rats. Blood pressure in hypertensive SHR is dose-dependently lowered by SAR407899 (1, 3, 10, and 30 mg/kg, oral) [1]. In healthy rabbits, penis length is increased by SAR407899 (1-3 mg/kg intravenously or 3, 10 mg/kg orally). In addition, SAR407899 (3–10 mg/kg, orally) lengthens the penis in diabetic rabbits in a dose-dependent manner [2].
In vivo, SAR-407899 demonstrates antihypertensive action in animals. Administration results in significant modulation of blood pressure in a dose-dependent manner. The compound shows good pharmacokinetic properties with adequate exposure to achieve therapeutic concentrations. Biomarker analyses confirm target engagement and pathway modulation in target tissues. |
| Enzyme Assay |
ROCK kinase activity is measured using radiometric or fluorescence-based assays with recombinant ROCK-2 enzyme and appropriate substrates. IC50 and Ki values are determined from dose-response curves. Selectivity profiling is conducted against a panel of 117 receptor and enzyme targets to establish the selectivity profile.
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| Cell Assay |
Cellular potency is evaluated in vascular smooth muscle cells by measuring ROCK-mediated phosphorylation and downstream signaling by Western blot or ELISA. Functional endpoints including vascular contraction and relaxation are measured to characterize the cellular activity of the compound.
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| Animal Protocol |
In vivo efficacy is evaluated in animal models of hypertension and microvascular angina. SAR-407899 is administered via appropriate routes at various doses. Blood pressure and other cardiovascular endpoints are monitored, and pharmacodynamic biomarkers are assessed in target tissues. Pharmacokinetic sampling is performed to correlate exposure with efficacy.
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| ADME/Pharmacokinetics |
SAR-407899 demonstrates favorable pharmacokinetic properties with adequate exposure for in vivo efficacy studies. Detailed PK parameters including half-life, clearance, and bioavailability are available from preclinical studies. The compound shows acceptable pharmacokinetic properties for cardiovascular indications.
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| Toxicity/Toxicokinetics |
Toxicology data for SAR-407899 are derived from preclinical safety studies. The compound shows an acceptable safety profile at therapeutic doses. Comprehensive toxicology assessments including genotoxicity, cardiotoxicity (hERG), and repeated-dose toxicity studies have been conducted as part of the development program.
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| References |
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| Additional Infomation |
SAR-407899 has been investigated in preclinical development for the treatment of microvascular angina (Syndrome X). The compound represents a promising therapeutic approach for cardiovascular diseases through ROCK inhibition. Development status and specific indications may vary, and the compound remains an important tool for studying ROCK biology and cardiovascular function.
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| Molecular Formula |
C14H16N2O2
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|---|---|
| Molecular Weight |
244.2890
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| Exact Mass |
244.121
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| CAS # |
923359-38-0
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| Related CAS # |
SAR407899 hydrochloride;923262-96-8
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| PubChem CID |
15604510
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
517.8±50.0 °C at 760 mmHg
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| Flash Point |
267.0±30.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.579
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| LogP |
1.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
337
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IPEXHQGMTHOKQV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H16N2O2/c17-14-13-2-1-12(9-10(13)3-8-16-14)18-11-4-6-15-7-5-11/h1-3,8-9,11,15H,4-7H2,(H,16,17)
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| Chemical Name |
6-piperidin-4-yloxy-2H-isoquinolin-1-one
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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 : ~6 mg/mL (~24.56 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0935 mL | 20.4675 mL | 40.9350 mL | |
| 5 mM | 0.8187 mL | 4.0935 mL | 8.1870 mL | |
| 10 mM | 0.4093 mL | 2.0467 mL | 4.0935 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.
Dose-dependent effect of intravenous SAR407899 on penile erection in normal rabbits.J Transl Med.2012 Mar 23;10:59. |
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Penile erection in diabetic rabbits after oral SAR407899 in comparison with sildenafil.J Transl Med.2012 Mar 23;10:59. |
Semilogaritmic plot of molar concentrations of SAR407899 against in vitro relaxation of human 3 μM phenylephrine-precontracted corpus cavernosum. |
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