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MedKoo Cat#: 526770 | Name: SAR407899 free base
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

SAR407899 is a potent and selective Rho kinase inhibitor with promising antihypertensive activity. SAR407899 potently inhibits endothelin-1-induced constriction of renal resistance arteries. SAR407899 is equipotent against human and rat-derived Rho-kinase 2 with inhibition constant values of 36 nM and 41 nM, respectively. SAR407899 is approximately 8-fold more active than fasudil. SAR407899 potently (mean IC(50) values: 122 to 280 nM) and species-independently relaxed precontracted isolated arteries of different species and different vascular beds. The antihypertensive effect of SAR407899 was superior to that of fasudil and Y-27632.

Chemical Structure

SAR407899 free base
SAR407899 free base
CAS#923359-38-0 (free base)

Theoretical Analysis

MedKoo Cat#: 526770

Name: SAR407899 free base

CAS#: 923359-38-0 (free base)

Chemical Formula: C14H16N2O2

Exact Mass: 244.1212

Molecular Weight: 244.29

Elemental Analysis: C, 68.83; H, 6.60; N, 11.47; O, 13.10

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
50mg USD 250.00 Ready to ship
100mg USD 450.00 Ready to ship
200mg USD 750.00 Ready to ship
500mg USD 1,650.00 Ready to ship
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Related CAS #
923262-96-8 (HCl) 923359-38-0 (free base)
Synonym
SAR407899; SAR 407899; SAR-407899; SAR407899 HCl
IUPAC/Chemical Name
6-(piperidin-4-yloxy)isoquinolin-1(2H)-one
InChi Key
IPEXHQGMTHOKQV-UHFFFAOYSA-N
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)
SMILES Code
O=C1NC=CC2=C1C=CC(OC3CCNCC3)=C2
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Related CAS# CAS#923262-96-8 (HCl); CAS#923359-38-0 (free base).
Biological target:
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.
In vitro activity:
Human aortic SMCs were starved overnight and after that stimulated with platelet-derived growth factor (10 ng/mL) and different concentration of the ROCK inhibitor for 12 hours. 5-Bromodeoxyuridine was added to the culture medium for 3 hours. SAR407899 concentration-dependently inhibited 5-bromodeoxyuridine incorporation into the cells (please see the online Data Supplement) with an IC50 of 5.0±1.3 μmol/L. In addition, the efficacy of SAR407899 in vitro on monocyte chemotactic protein-1–induced chemotaxis of human THP-1 monocytoid cells has been tested. SAR407899 effectively inhibited THP-1 migration (please see the online Data Supplement) with an IC50 of 2.5±1.0 μmol/L. Reference: Hypertension. 2009 Sep;54(3):676-83. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.109.134353?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
In vivo activity:
SAR407899 (orally at 1, 3, 10, and 30 mg/kg) dose dependently lowered blood pressure in hypertensive SHRs (Figure 4C) without marked changes in heart rate except for the highest dose (Figure 4D). In normotensive WKY rats, SAR407899 at 3 and 10 mg/kg PO produced a nonsignificant blood pressure–lowering effect (Figure 4A), whereas administration of 30 mg/kg of SAR407899 decreased blood pressure by ≈15 mm Hg associated with a tachycardia (Figure 4B). The pharmacokinetic profile of SAR407899 was compared in these 2 strains. As shown in Figure 4G, the plasma levels of SAR407899 were practically identical both in terms of maximum capacity and kinetics in both strains. In hypertensive dTg hRen-hAgt mice, PO administration of SAR407899 at 10 mg/kg caused a marked decrease of mean arterial blood pressure by ≈70 mm Hg (Figure 4E). Interestingly, despite this significant blood pressure reduction, no effect on heart rate was observed (Figure 4F). Reference: Hypertension. 2009 Sep;54(3):676-83. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.109.134353?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Solvent mg/mL mM
Solubility
DMSO 6.0 24.56
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 244.29 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
1. Löhn M, Plettenburg O, Ivashchenko Y, Kannt A, Hofmeister A, Kadereit D, Schaefer M, Linz W, Kohlmann M, Herbert JM, Janiak P, O'Connor SE, Ruetten H. Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. Hypertension. 2009 Sep;54(3):676-83. doi: 10.1161/HYPERTENSIONAHA.109.134353. Epub 2009 Jul 13. PMID: 19597037.
In vivo protocol:
1. Löhn M, Plettenburg O, Ivashchenko Y, Kannt A, Hofmeister A, Kadereit D, Schaefer M, Linz W, Kohlmann M, Herbert JM, Janiak P, O'Connor SE, Ruetten H. Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. Hypertension. 2009 Sep;54(3):676-83. doi: 10.1161/HYPERTENSIONAHA.109.134353. Epub 2009 Jul 13. PMID: 19597037. 2. Löhn M, Plettenburg O, Kannt A, Kohlmann M, Hofmeister A, Kadereit D, Monecke P, Schiffer A, Schulte A, Ruetten H, Ivashchenko Y. End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899. World J Cardiol. 2015 Jan 26;7(1):31-42. doi: 10.4330/wjc.v7.i1.31. PMID: 25632317; PMCID: PMC4306204.
1: Löhn M, Plettenburg O, Kannt A, Kohlmann M, Hofmeister A, Kadereit D, Monecke P, Schiffer A, Schulte A, Ruetten H, Ivashchenko Y. End-organ protection in hypertension by the novel and selective Rho-kinase inhibitor, SAR407899. World J Cardiol. 2015 Jan 26;7(1):31-42. doi: 10.4330/wjc.v7.i1.31. PubMed PMID: 25632317; PubMed Central PMCID: PMC4306204. 2: Babelova A, Jansen F, Sander K, Löhn M, Schäfer L, Fork C, Ruetten H, Plettenburg O, Stark H, Daniel C, Amann K, Pavenstädt H, Jung O, Brandes RP. Activation of Rac-1 and RhoA contributes to podocyte injury in chronic kidney disease. PLoS One. 2013 Nov 7;8(11):e80328. doi: 10.1371/journal.pone.0080328. eCollection 2013. PubMed PMID: 24244677; PubMed Central PMCID: PMC3820652. 3: Guagnini F, Ferazzini M, Grasso M, Blanco S, Croci T. Erectile properties of the Rho-kinase inhibitor SAR407899 in diabetic animals and human isolated corpora cavernosa. J Transl Med. 2012 Mar 23;10:59. doi: 10.1186/1479-5876-10-59. PubMed PMID: 22444253; PubMed Central PMCID: PMC3328245. 4: Grisk O, Schlüter T, Reimer N, Zimmermann U, Katsari E, Plettenburg O, Löhn M, Wollert HG, Rettig R. The Rho kinase inhibitor SAR407899 potently inhibits endothelin-1-induced constriction of renal resistance arteries. J Hypertens. 2012 May;30(5):980-9. doi: 10.1097/HJH.0b013e328351d459. PubMed PMID: 22388233. 5: Löhn M, Plettenburg O, Ivashchenko Y, Kannt A, Hofmeister A, Kadereit D, Schaefer M, Linz W, Kohlmann M, Herbert JM, Janiak P, O'Connor SE, Ruetten H. Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. Hypertension. 2009 Sep;54(3):676-83. doi: 10.1161/HYPERTENSIONAHA.109.134353. Epub 2009 Jul 13. PubMed PMID: 19597037.