In vitro: Hydroxyfasudil prevents the downregulation of endothelial NO synthase (eNOS) under hypoxic conditions. In a concentration-dependent manner, hydroxyfasudil increases eNOS mRNA and protein expression, resulting in a 1.9- and 1.6-fold increase, respectively, at 10 μmol/L (P<0.05 for both). This correlates with a 1.5- and 2.3-fold increase in eNOS activity and NO production, respectively (P<0.05 for both). Hydroxyfasudil also inhibits various chemoattractant-induced migration of neutrophils. Hydroxyfasudil potently inhibits Rho-kinase (IC50, 0.9 ± 1.8 μM), while its inhibitory effect is markedly (at least 50 ± 100 times) less for myosin light chain kinase (MLCK) or protein kinase C (PKC).
In vivo: Intracoronary administration of hydroxyfasudil(HF) causes a significant coronary vasodilation of both small arteries and arterioles in a dose-dependent manner under control conditions with a resultant increase in CBF(coronary blood flow). Intracoronary hydroxyfasudil does not significantly alter mean aortic pressure or heart rate. Pretreatment with hydroxyfasudil markedly reduces the I/R-induced myocardial infarct size, and this beneficial effect of hydroxyfasudil is significantly attenuated by L-NMMA. NO may be involved in those cardiovascular protective effects of hydroxyfasudil. Hydroxyfasudil may also be effective for the treatment of pulmonary hypertension. HF protects the myocardium subjected to pacing-induced ischaemia through the increase in the regional myocardial blood flow.
|Cell lines||Human vascular endothelial cells|
|Preparation method||Human vascular endothelial cells are treated with increasing concentrations of hydroxyfasudil (0.1 to 100 μmol/L) and eNOS expression and activity are measured.|
|Concentrations||0.1 to 100 μmol/L|
|Incubation time||18 h|
|Animal models||Mongrel dogs|
|Dosages||10, 30, and 100 μg/kg|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO: ≥ 30 mg/mL|
Protective effect of hydroxyfasudil, a Rho kinase inhibitor, on ventral prostatic hyperplasia in the spontaneously hypertensive rat.
Holmström F, et al. Prostate. 2015 Nov;75(15):1774-82. PMID: 26286428.
Effects of the Rho kinase inhibitor, hydroxyfasudil, on bladder dysfunction and inflammation in rats with HCl-induced cystitis.
Shimizu N, et al. Int J Urol. 2013 Nov;20(11):1136-43. PMID: 23419011.
|Related ROCK Products|
ZINC00881524 is a potent and selective ROCK inhibitor.
|Ripasudil (K-115) dihydrate
Ripasudil (K-115) hydrochloride dihydrate is potent ROCK inhibitor with IC50 of 51 nM and 19 nM for ROCK1 and ROCK2, respectively, used for the treatment of glaucoma and ocular hypertension.
SR-3677 is a new potent and selective ROCK-II inhibitor with an IC50 of ~3 nM in enzyme and cell based assays; IC50 for ROCK-I is 56 ± 12 nM.
GSK180736A, developed as a Rho-associated, coiled-coil-containing protein kinase inhibitor, binds to GRK2(G protein-coupled receptor kinase 2) with logIC50 pf -6.6 (logIC50 -4.0 for GRK5 and >-3 for GRK1); ≥400-fold selective for GRK2 over both GRK1 and GRK5.
GSK269962A is a potent ROCK inhibitor with IC50 values of 1.6 and 4 nM for recombinant human ROCK1 and ROCK2, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.