Fasudil Hydrochloride, a potent Rho-kinase inhibitor and vasodilator.

Fasudil, also known as HA-1077, is a potent Rho-kinase inhibitor and vasodilator. Fasudil has been used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage, as well as to improve the cognitive decline seen in stroke victims. It has been found to be effective for the treatment of pulmonary hypertension. It was demonstrated in February 2009 that fasudil could also be used to enhance memory and improve the prognosis of Alzheimers patients. It is approved for use in Japan and China.

Product information

CAS Number: 105628-07-7

Molecular Weight: 327.83

Formula: C14H18ClN3O2S

Synonym:

HA-1077 HCl

Fasudil hydrochloride.

Related CAS Number:

105628-07-7 (HCl)

103745-39-7 (free base)

Chemical Name: 5-((1,4-diazepan-1-yl)sulfonyl)isoquinoline hydrochloride

Smiles: Cl.O=S(=O)(C1=CC=CC2=CN=CC=C21)N1CCCNCC1

InChiKey: LFVPBERIVUNMGV-UHFFFAOYSA-N

InChi: InChI=1S/C14H17N3O2S.ClH/c18-20(19,17-9-2-6-15-8-10-17)14-4-1-3-12-11-16-7-5-13(12)14;/h1,3-5,7,11,15H,2,6,8-10H2;1H

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO, not in water

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:

Fasudil Hydrochloride (100 μM) inhibits cell spreading, the formation of stress fibers, and expression of α-SMA with concomitant suppression of cell growth in rat HSCs and human HSC-derived TWNT-4 cells. Fasudil Hydrochloride (50-100 μM; 24 hours) inhibits the LPA-induced phosphorylation of ERK1/2, JNK, and p38 detected by western blotting in rat HSCs and human HSC-derived TWNT-4 cells. Fasudil Hydrochloride (25-100 μM; 24 hours) suppresses transcription of collagen and TIMP, stimulates transcription of MMP-1 in human HSC-derived TWNT-4 cells.

In Vivo:

Fasudil (30 μg) increases CBF by 50% via intra-coronary injection to dogs. Fasudil (0.01, 0.03, 0.1 and 0.3 mg/kg, bolus, i.v.) decreases MBP and increases HR, VBF, CBF, RBF, and FBF. Fasudil (1.0 ng/mL) increases cardiac output. Fasudil via i.v. produces a significant fall in MBP, left ventricular systolic pressure and total peripheral resistance with an increase in HR and cardiac output, but without obvious effect on right atrial pressure, dP/dt or left ventricular minute work in dogs. Fasudil exhibits protectable effects on cardiovascular disease and reduces the activation of JNK and attenuates mitochondrial-nuclear translocation of AIF under ischemic injury. Fasudil (100 mg/kg/day, p.o.) significantly reduces incidence and mean maximum clinical score of EAE in SJL/J mice immunized with PLP p139-151. Fasudil inhibits the proliferative response of splenocytes to the antigen in mice. Fasudil decreases inflammation, demyelination, axonal loss and APP positivein spinal cord of Fasudil-treated mice via p.o. administration.

References:

1. Shi J, Wei L. Rho kinases in cardiovascular physiology and pathophysiology: the effect of fasudil. J Cardiovasc Pharmacol. 2013 Oct;62(4):341-54. doi: 10.1097/FJC.0b013e3182a3718f. Review. PubMed PMID: 23921309; PubMed Central PMCID: PMC3884946.
2. Chen M, Liu A, Ouyang Y, Huang Y, Chao X, Pi R. Fasudil and its analogs: a new powerful weapon in the long war against central nervous system disorders? Expert Opin Investig Drugs. 2013 Apr;22(4):537-50. doi: 10.1517/13543784.2013.778242. Epub 2013 Mar 5. Review. PubMed PMID: 23461757.
3. Raja SG. Evaluation of clinical efficacy of fasudil for the treatment of pulmonary arterial hypertension. Recent Pat Cardiovasc Drug Discov. 2012 Aug;7(2):100-4. Review. PubMed PMID: 22670803.
4. Kitazono T. [Fasudil hydrochloride]. Nihon Rinsho. 2006 Oct 28;64 Suppl 7:617-21. Review. Japanese. PubMed PMID: 17461215.
5. Ishida T, Takanashi Y, Kiwada H. Safe and efficient drug delivery system with liposomes for intrathecal application of an antivasospastic drug, fasudil. Biol Pharm Bull. 2006 Mar;29(3):397-402. Review. PubMed PMID: 16508135.

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