[CAS NO. 923262-96-8] SAR407899hydrochloride
PRODUCTS SPECIFICATIONS [923262-96-8]
DESCRIPTION [923262-96-8]
Overview
| MDL | MFCD20485429 |
|---|---|
| Molecular Weight | 280.75 |
| Molecular Formula | C14H17ClN2O2 |
| SMILES | O=C(NC=C1)C(C1=C2)=CC=C2OC3CCNCC3.[H]Cl |
2 Publications Citing Use of MCE
Summary
SAR407899 hydrochloride is a selective, potent and ATP-competitive ROCK inhibitor, with an IC 50 of 135 nM for ROCK-2 , and K i s of 36 nM and 41 nM for human and rat ROCK-2 , respectively.
IC50 & Target
|
ROCK-2 102 nM (IC 50 ) |
ROCK-1 276 nM (IC 50 ) |
In Vitro
SAR407899 hydrochloride is a potent and ATP-competitive ROCK inhibitor, with K i s of 36 nM and 41 nM for human and rat ROCK-2, respectively. SAR407899 inhibits ROCK-2 better than ROCK-1, with IC 50 s 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 IC 50 s 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 MYPT T696 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 IC 50 of 5.0±1.3 μM. SAR407899 also effectively inhibits THP-1 migration with an IC 50 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 IC 50 values between 122 and 280 nM [1] . SAR407899 dose-dependently relaxes the phenylephrine pre-contracted smooth muscle, with IC 50 s of 0.07 and 0.05 μM, respectively [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
SAR407899 (3 mg/kg, i.v.) inhibits ROCK-mediated phosphorylation of MYPT T696 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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00914277 | Sanofi |
Erectile Dysfunction
|
May 2009 | Phase 2 |
| NCT03236311 | Sanofi |
Microvascular Coronary Artery Disease
|
October 12, 2017 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
H 2 O : 50 mg/mL ( 178.09 mM ; Need ultrasonic)
DMSO : 25 mg/mL ( 89.05 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.5619 mL | 17.8094 mL | 35.6189 mL |
| 5 mM | 0.7124 mL | 3.5619 mL | 7.1238 mL |
| 10 mM | 0.3562 mL | 1.7809 mL | 3.5619 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 25 mg/mL (89.05 mM); Clear solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (8.90 mM); Clear solution
-
4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (8.90 mM); Clear solution
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.