Introduction：Basic information about CAS 923262-96-8|SAR407899 (hydrochloride), including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | SAR407899 (hydrochloride) |
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| CAS Number | 923262-96-8 | Molecular Weight | 280.75000 |
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| Density | / | Boiling Point | / |
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| Molecular Formula | C14H17ClN2O2 | Melting Point | / |
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| MSDS | / | Flash Point | / |
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Names
| Name | 6-piperidin-4-yloxy-2H-isoquinolin-1-one,hydrochloride |
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| Synonym | More Synonyms |
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SAR407899 (hydrochloride) BiologicalActivity
| 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. |
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| Related Catalog | Signaling Pathways >>Cell Cycle/DNA Damage >>ROCKSignaling Pathways >>Stem Cell/Wnt >>ROCKSignaling Pathways >>TGF-beta/Smad >>ROCKResearch Areas >>Metabolic Disease |
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| Target | ROCK-2:102 nM (IC50) ROCK-1:276 nM (IC50) |
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| 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]. |
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| 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]. |
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| 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]. |
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| References | [1]. L?hn M, et al. Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. Hypertension. 2009 Sep;54(3):676-83. [2]. Guagnini F, et al. Erectile properties of the Rho-kinase inhibitor SAR407899 in diabetic animals and human isolated corpora cavernosa. J Transl Med. 2012 Mar 23;10:59. [3]. Chen W, et al. Screening RhoA/ROCK inhibitors for the ability to prevent chronic rejection of mouse cardiac allografts.Transpl Immunol. 2018 Jun 6. pii: S0966-3274(18)30029-7. |
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Chemical & Physical Properties
| Molecular Formula | C14H17ClN2O2 |
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| Molecular Weight | 280.75000 |
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| Exact Mass | 280.09800 |
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| PSA | 54.12000 |
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| LogP | 2.78970 |
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Safety Information
Customs
| HS Code | 2933990090 |
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| 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% |
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Synonyms
| qc-9996 |
| SAR407899 |
| SAR407899 (hydrochloride) |
