923262-96-8
923262-96-8 structure
- Name: SAR407899 (hydrochloride)
- Chemical Name: 6-piperidin-4-yloxy-2H-isoquinolin-1-one,hydrochloride
- CAS Number: 923262-96-8
- Molecular Formula: C14H17ClN2O2
- Molecular Weight: 280.75000
- Catalog: Signaling Pathways Cell Cycle/DNA Damage ROCK
- Create Date: 2018-11-26 18:14:35
- Modify Date: 2024-01-14 02:01:50
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SAR407899 hydrochloride 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-piperidin-4-yloxy-2H-isoquinolin-1-one,hydrochloride |
|---|---|
| Synonyms |
qc-9996
SAR407899 SAR407899 (hydrochloride) |
| Description | SAR407899 hydrochloride 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 hydrochloride 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 |
| Molecular Formula | C14H17ClN2O2 |
|---|---|
| Molecular Weight | 280.75000 |
| Exact Mass | 280.09800 |
| PSA | 54.12000 |
| LogP | 2.78970 |
| HS Code | 2933990090 |
|---|
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923262-96-8 |
| Literature: SANOFI; GESSLER, Dr., Simon; WOLLMANN, Dr., Theo Patent: WO2013/7502 A1, 2013 ; Location in patent: Page/Page column 22 ; |
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923262-96-8 |
| Literature: SANOFI-AVENTIS Patent: WO2008/77550 A1, 2008 ; Location in patent: Page/Page column 62-63 ; WO 2008/077550 A1 |
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923262-96-8 |
| Literature: SANOFI; GESSLER, Dr., Simon; WOLLMANN, Dr., Theo Patent: WO2013/7502 A1, 2013 ; |
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923262-96-8 |
| Literature: SANOFI; GESSLER, Dr., Simon; WOLLMANN, Dr., Theo Patent: WO2013/7502 A1, 2013 ; |
| HS Code | 2933990090 |
|---|---|
| Summary | 2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0% |