Hydroxyfasudil HCl

Hydroxyfasudil, aslo known as HA1100, is a cell-permeable hydroxylated metabolite of HA-1077, is a potent inhibitor of Rho-associated kinase (ROCK) (Ki = 150 nM). Hydroxyfasudil alleviates demyelination through the inhibition of MOG antibody and microglia activation in cuprizone mouse model.

Product information

CAS Number: 155558-32-0

Molecular Weight: 343.83

Formula: C14H18ClN3O3S

Synonym:

HA-1100 HCl

HA 1100

Hydroxyfasudil hydrochloride

Related CAS Number:

105628-72-6 (Hydroxyfasudil free base)

Chemical Name: 1-(1-Hydroxy-5-isoquinolinesulfonyl)homopiperazine hydrochloride

Smiles: Cl.OC1=NC=CC2C1=CC=CC=2S(=O)(=O)N1CCCNCC1

InChiKey: XWWFOUVDVJGNNG-UHFFFAOYSA-N

InChi: InChI=1S/C14H17N3O3S.ClH/c18-14-12-3-1-4-13(11(12)5-7-16-14)21(19,20)17-9-2-6-15-8-10-17;/h1,3-5,7,15H,2,6,8-10H2,(H,16,18);1H

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Hydroxyfasudil hydrochloride is a ROCK inhibitor, with IC50s of 0.73 and 0.72 μM for ROCK1 and ROCK2, respectively. Hydroxyfasudil also less potently inhibits PKA, with an IC50 of 37 μM, 50-fold higher than those of the ROCKs. Hydroxyfasudil increases eNOS mRNA levels, with an EC50 value of 0.8 ± 0.3 μM. Hydroxyfasudil (0-100 μM) concentration-dependently increases eNOS activity and stimulates NO production in human aortic endothelial cells (HAEC). Hydroxyfasudil (10 μM) increases the half-life of eNOS mRNA from 13 to 16 hours, but does not affect eNOS promoter activity at concentrations from 0.1 to 100 μM.

In Vivo:

Hydroxyfasudil (10 mg/kg, i.p.) significantly increases both the average and maximal voided volumes in SD rats. Hydroxyfasudil also significantly decreases the maximal detrusor pressure. Hydroxyfasudil (3 mg/kg, i.p) inhibits hypercontractility induced by norepinephrine in spontaneously hypertensive rats (SHRs). Furthermore, Hydroxyfasudil (3, 10 mg/kg, i.p) significantly ameliorates decreased penile cGMP contents in rats.

References:

1. Wang J, Sui RX, Miao Q, Wang Q, Song LJ, Yu JZ, Li YH, Xiao BG, Ma CG. Hydroxyfasudil alleviates demyelination through the inhibition of MOG antibody and microglia activation in cuprizone mouse model. Clin Immunol. 2019 Apr;201:35-47. doi: 10.1016/j.clim.2019.01.006. Epub 2019 Jan 17. PubMed PMID: 30660624.
2. Antolín AA, Mestres J. Dual Inhibitors of PARPs and ROCKs. ACS Omega. 2018 Oct 31;3(10):12707-12712. doi: 10.1021/acsomega.8b02337. Epub 2018 Oct 5. PubMed PMID: 30411017; PubMed Central PMCID: PMC6210072.
3. Bozkurt A, Budak H, Erol HS, Can S, Mercantepe T, Akin Y, Ozbey I, Cankaya M, Halici MB, Coban TA. A novel therapeutics agent: antioxidant effects of hydroxylfasudil on rat kidney and liver tissues in a protamine sulphate-induced cystitis rat model; preliminary results. Artif Cells Nanomed Biotechnol. 2018;46(sup2):9-14. doi: 10.1080/21691401.2018.1449120. Epub 2018 Mar 9. PubMed PMID: 29523028.
4. Vieira GM, Roberto GM, Lira RC, Engel EE, Tone LG, Brassesco MS. Prognostic value and functional role of ROCK2 in pediatric Ewing sarcoma. Oncol Lett. 2018 Feb;15(2):2296-2304. doi: 10.3892/ol.2017.7571. Epub 2017 Dec 8. PubMed PMID: 29434937; PubMed Central PMCID: PMC5777092.
5. Cheng CI, Lee YH, Chen PH, Lin YC, Chou MH, Kao YH. Cobalt chloride induces RhoA/ROCK activation and remodeling effect in H9c2 cardiomyoblasts: Involvement of PI3K/Akt and MAPK pathways. Cell Signal. 2017 Aug;36:25-33. doi: 10.1016/j.cellsig.2017.04.013. Epub 2017 Apr 21. PubMed PMID: 28435089.

Products are for research use only. Not for human use.