"目录号: HY-13911

Cell Cycle/DNA DamageTGF-beta/SmadStem Cell/Wnt-

Hydroxyfasudil(HA1100)是Fasudil的代谢物，对ROCK1和ROCK2的IC50分别为120nM和170nM，还是血管舒张剂。

ROCK

相关产品

Y-27632 dihydrochloride-SLx-2119-Y-33075 dihydrochloride-Narciclasine-GSK269962A-Fasudil Hydrochloride-GSK429286A-LX7101-ROCK inhibitor-Thiazovivin-SR-3677-K-115-RKI-1447-chroman 1-H-1152 dihydrochloride-

生物活性

Description

Hydroxyfasudil(HA1100), metabolite of Fasudil, is a potent Rho-kinase inhibitor and vasodilator.IC50 Value: 0.12 uM (ROCK1); 0.17 uM (ROCK2) [1]Target: ROCKin vitro: Fasudil (1-10 μM) and hydroxyfasudil (0.3-10 μM) significantly prevented endothelin-induced cardiomyocyte hypertrophy [2]. Hydroxyfasudil significantly attenuated serotonin (IC)-induced vasoconstriction of SA (-7 +/- 1% vs. 2 +/- 1%, p < 0.01). Coronary I/R significantly impaired coronary vasodilation to acetylcholine after I/R (SA, p < 0.05; and A, p < 0.01 vs. before I/R) and L-NMMA further reduced the vasodilation, whereas hydroxyfasudil completely preserved the responses.in vivo: Treatment with hydroxyfasudil significantly improved bladder intercontraction intervals. Rats treated with hydroxyfasudil also showed a significant reduction of histopathological features associated with cystitis [3]. Twelve-week-old male SHRs were treated with hydroxyfasudil (3 or 10 mg/kg, i.p.) once a day for 6 weeks. Treatment with hydroxyfasudil significantly improved the decreased penile cGMP concentrations, the increased Rho kinase activities, the increased norepinephrine-induced contractions, and the decreased acetylcholine-induced relaxation in a dose-dependent manner [4]. Toxicity: The proportion of patients with good clinical outcome was 74.5% (41/55) in the fasudil group and 61.7% (37/60) in the nimodipine group. There were no serious adverse events reported in the fasudil group [5]. Clinical trial: N/A

References

[1].Tsutomu Akama, et al. Linking Phenotype to Kinase: Identification of a Novel Benzoxaborole Hinge Binding Motif for Kinase Inhibition and the Development of High Potency Rho-Kinase Inhibitors. JPET Fast Forward. Published on September 18, 2013.

[2].Satoh S, et al. Evidence of a direct cellular protective effect of Rho-kinase inhibitors on endothelin-induced cardiac myocyte hypertrophy. Biochem Biophys Res Commun. 2012 Jul 27;424(2):338-40.

[3].Shimizu N, et al. Effects of the Rho kinase inhibitor, hydroxyfasudil, on bladder dysfunction and inflammation in rats with HCl-induced cystitis. Int J Urol. 2013 Feb 19.

[4].Saito M, et al. Hydroxyfasudil ameliorates penile dysfunction in the male spontaneously hypertensive rat. Pharmacol Res. 2012 Oct;66(4):325-31.

[5].Zhao J, et al. Efficacy and safety of fasudil in patients with subarachnoid hemorrhage: final results of a randomized trial offasudil versus nimodipine. Neurol Med Chir (Tokyo). 2011;51(10):679-83.