923359-38-0
923359-38-0 structure
- Name: SAR-407899
- Chemical Name: 6-(4-Piperidinyloxy)-1(2H)-isoquinolinone
- CAS Number: 923359-38-0
- Molecular Formula: C14H16N2O2
- Molecular Weight: 244.289
- Catalog: Signaling Pathways Cell Cycle/DNA Damage ROCK
- Create Date: 2018-07-25 21:48:02
- Modify Date: 2024-01-31 23:15:59
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SAR407899 is a selective, potent and ATP-competitive ROCK inhibitor, with an IC50 of 135 nM for ROCK-2, and Kis of 36 nM and 41 nM for human and rat ROCK-2, respectively.
| Name | 6-(4-Piperidinyloxy)-1(2H)-isoquinolinone |
|---|---|
| Synonyms |
SAR-407899
1(2H)-Isoquinolinone, 6-(4-piperidinyloxy)- 6-(4-Piperidinyloxy)-1(2H)-isoquinolinone 6-(piperidin-4-yloxy)-2H-isoquinolin-1-one SAR407899 |
| Description | SAR407899 is a selective, potent and ATP-competitive ROCK inhibitor, with an IC50 of 135 nM for ROCK-2, and Kis of 36 nM and 41 nM for human and rat ROCK-2, respectively. |
|---|---|
| Related Catalog | |
| Target |
ROCK-2:102 nM (IC50) ROCK-1:276 nM (IC50) |
| In Vitro | SAR407899 is a potent and ATP-competitive ROCK inhibitor, with Kis of 36 nM and 41 nM for human and rat ROCK-2, respectively. SAR407899 inhibits ROCK-2 better than ROCK-1, with IC50s of 102 ± 19 nM and 276 ± 26 nM, respectively, in the presence of 40 μM ATP. SAR407899 also less potently inhibits PKC-Δ and MSK-1, with IC50s of 5.4 and 3.1 μM, respectively. SAR407899 (0.1, 0.3, 1.0, and 3.0 μM) specifically inhibits the ROCK-mediated phosphorylation of MYPTT696 in HeLa cells stimulated with PHEN, and shows such effects at 1 μM and 10 μM in primary rat aortic smooth muscle cells. SAR407899 (3 μM) completely blocks thrombin-induced shrinkage of human umbilical vein endothelial cells (HUVECs) and stress fiber formation. SAR407899 concentration-dependently inhibits 5-bromodeoxyuridine incorporation into the cells with an IC50 of 5.0 ± 1.3 μM. SAR407899 also effectively inhibits THP-1 migration with an IC50 of 2.5 ± 1.0 μM. SAR407899 shows a potent vasorelaxant activity in a broad variety of isolated arteries taken from different vascular beds and species, with a range of IC50 values between 122 and 280 nM[1]. SAR407899 dose-dependently relaxes the phenylephrine pre-contracted smooth muscle, with IC50s of 0.07 and 0.05 μM, respectively[2]. |
| In Vivo | SAR407899 (3 mg/kg, i.v.) inhibits ROCK-mediated phosphorylation of MYPTT696 in thoracic aorta of spontaneously hypertensive rats (SHRs). SAR407899 (0.01-0.30 mg/kg, i.v.) efficiently reduces pressor responses to vasoconstrictor agents in rats. SAR407899 (1, 3, 10, and 30 mg/kg, p.o.) dose dependently lowers blood pressure in hypertensive SHRs[1]. SAR407899 (1-3 mg/kg, i.v. or 3, 10 mg/kg, p.o.) increases the length of the penis in healthy rabbits. SAR407899 (3-10 mg/kg, p.o.) also dose-dependently increases penile length in diabetic rabbits[2]. |
| Animal Admin | Rabbits are treated either intravenously (i.v., in an ear vein) with increasing doses of SAR407899 (0.3, 1, 3, 10 mg/kg) or orally with SAR407899 (1, 3, 10, 30 mg/kg) or sildenafil (2 or 6 mg/kg). Each animal is used several times for different doses and different agents, always with a week's washout. The length (mm) of uncovered penile mucosa (penile erection parameter) is measured at different time-points, using a sliding digital caliper. The results are expressed as mean ± SEM penile length of 3-5 rabbits[2]. |
| References |
| Density | 1.2±0.1 g/cm3 |
|---|---|
| Boiling Point | 517.8±50.0 °C at 760 mmHg |
| Molecular Formula | C14H16N2O2 |
| Molecular Weight | 244.289 |
| Flash Point | 267.0±30.1 °C |
| Exact Mass | 244.121185 |
| PSA | 54.12000 |
| LogP | 1.10 |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C |
| Index of Refraction | 1.579 |