SAR407899 hydrochloride

• CAT Number: I005490
• CAS Number: 923262-96-8
• Molecular Formula: C14H17ClN2O2
• Molecular Weight: 280.75
• Purity: ≥95%
• Synonyms: 6-(piperidin-4-yloxy)isoquinolin-1(2H)-one hydrochloride
• Target: ROCK
• Solubility: DMSO: ≥ 2.8 mg/mL, DMSO: ＜ 8.2 mg/mL
• Storage: Store at -20°C
• IC50: 36 nM/41 nM(Ki, human/Rat ROCK)

SAR407899 Hcl is a potent, ATP-competitive ROCK inhibitor woth Ki value of 36 nM/41 nM for human ROCK/Rat ROCK respectively. 


in vitro: SAR407899 is highly selective in panel of 117 receptor and enzyme targets. SAR407899 is ≈8-fold more active than fasudil. In vitro, SAR407899 demonstrated concentration-dependent inhibition of Rho-kinase–mediated phosphorylation of myosin phosphatase, thrombin-induced stress fiber formation, platelet-derived growth factor–induced proliferation, and monocyte chemotactic protein-1–stimulated chemotaxis. SAR407899 potently (mean IC50 values: 122 to 280 nM) and species-independently relaxed precontracted isolated arteries of different species and different vascular beds [1]. SAR407899 dose-dependently relaxed the pre-contracted corpora cavernosa in all species, with similar potency and efficacy in healthy vs diabetic rats, WKY vs SHR rats, healthy vs diabetic rabbits (IC(50) range from 0.05 to 0.29 μM, Emax range 89 to 97%) [3]. 


in vivo: Over the dose range 3 to 30 mg/kg PO, SAR407899 lowered blood pressure in a variety of rodent models of arterial hypertension [1]. SAR407899 was more effective than Y27632 in reducing ET-1-induced vasoconstriction in ZDF rat renal resistance arteries. Maximum ET-1-induced vasoconstriction in SAR407899-treated and Y27632-treated human renal resistance arteries was 23±5 and 48±6% of control values, respectively [2].

Reference

[1]. Lohn M, et al. Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. Hypertension. 2009 Sep;54(3):676-83. 


[2]. Grisk O, et al. The Rho kinase inhibitor SAR407899 potently inhibits endothelin-1-induced constriction of renal resistance arteries. J Hypertens. 2012 May;30(5):980-9. 


[3]. 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.