CAS 105628-07-7|Fasudil Hydrochloride

Introduction：Basic information about CAS 105628-07-7|Fasudil Hydrochloride, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Fasudil Hydrochloride BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Customs
7. Synonyms

Common Name	Fasudil Hydrochloride
CAS Number	105628-07-7	Molecular Weight	327.83
Density	/	Boiling Point	506.2ºC at 760 mmHg
Molecular Formula	C₁₄H₁₈ClN₃O₂S	Melting Point	222 °C(dec.)
MSDS	/	Flash Point	259.9ºC

Names

Name	Fasudil Hydrochloride
Synonym	More Synonyms

Fasudil Hydrochloride BiologicalActivity

Description	Fasudil Hydrochloride is a potent inhibitor of ROCK1, PKA, PKC, and MLCK with Kis of 0.33 μM, 1.0 μM, 9.3 μM and 55 μM, respectively.
Related Catalog	Signaling Pathways >>Autophagy >>AutophagySignaling Pathways >>Protein Tyrosine Kinase/RTK >>PKASignaling Pathways >>Stem Cell/Wnt >>PKASignaling Pathways >>Cell Cycle/DNA Damage >>ROCKSignaling Pathways >>Stem Cell/Wnt >>ROCKSignaling Pathways >>TGF-beta/Smad >>ROCKResearch Areas >>Cancer
Target	p160ROCK:0.33 μM (Ki) PKA:1 μM (Ki) PKC:9.3 μM (Ki) MLCK:55 μM (Ki)
In Vitro	Fasudil Hydrochloride has vasodilatory action and occupies the adenine pocket of the ATP-binding site of the enzyme[1]. Fasudil produces a competitive inhibition of the Ca2+-induced contraction of the depolarized rabbit aorta. Fasudil inhibits contractile responses to KCl, phenylephnne (PHE) and prostaglandin (PG) F2a[2]. Fasudil also exhibits vasodilator actions by inhibition of 5-hydroxytryptamine, noradrenaline, histamine, angiotensin, and dopamine induced spiral strips contraction[3]. In addition, Fasudil induces disorganization of actin stress fiber and cell migration inhibition[4]. Fasudil inhibits hepatic stellate cells spreading, the formation of stress fibers, and expression of α-SMA with concomitant suppression of cell growth, but does not induce apoptosis. Fasudil also blocks the LPA-induced phosphorylation of ERK1/2, JNK and p38 MAPK[5].
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[3]. Fasudil exhibits protectable effects on cardiovascular disease and reduces the activation of JNK and attenuates mitochondrial-nuclear translocation of AIF under ischemic injury[6]. 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[7].
Kinase Assay	Cyclic AMP-dependent protein kinase activity is assayed in a reaction mixture containing, in a final volume of 0.2 mL, 50 mM Tris-HCl (pH 7.0), 10 mM magnesium acetate, 2 mM EGTA, 1 μM cyclic AMP or absence of cyclic AMP, 3.3 to 20 μM [r-32P] ATP (4×105 c.p.m.), 0.5 μg of the enzyme, 100 μg of histone H2B and compound. The mixture is incubated at 30°C for 5 min. The reaction is terminated by adding 1mL of ice-cold 20% trichloroacetic acid after adding 500 μg of bovine serum albumin as a carrier protein. The sample is centrifuged at 3000 r.p.m. for 15min, the pellet is resuspended in ice-cold 10% trichloro-acetic acid solution and the centrifugation-resuspension cycle is repeated three times. The final pellet is dissolved in 1 mL of 1 N NaOH and radioactivity is measured with a liquid scintillation counter.
References	[1]. Ono-Saito N, et al. H-series protein kinase inhibitors and potential clinical applications. Pharmacol Ther. 1999 May-Jun;82(2-3):123-31. [2]. Asano T, et al. Mechanism of action of a novel antivasospasm drug, HA1077. J Pharmacol Exp Ther. 1987 Jun;241(3):1033-40. [3]. Asano T, et al. Vasodilator actions of HA1077 in vitro and in vivo putatively mediated by the inhibition of protein kinase. Br J Pharmacol. 1989 Dec;98(4):1091-100. [4]. Negoro N, et al. The kinase inhibitor fasudil (HA-1077) reduces intimal hyperplasia through inhibiting migration and enhancing cell loss of vascular smooth muscle cells. Biochem Biophys Res Commun. 1999 Aug 19;262(1):211-5. [5]. Fukushima M, et al. Fasudil hydrochloride hydrate, a Rho-kinase (ROCK) inhibitor, suppresses collagen production and enhances collagenase activity in hepatic stellate cells. Liver Int. 2005 Aug;25(4):829-38. [6]. Zhang J, et al. Inhibition of the activity of Rho-kinase reduces cardiomyocyte apoptosis in heart ischemia/reperfusion via suppressing JNK-mediated AIF translocation. Clin Chim Acta. 2009 Mar;401(1-2):76-80. [7]. Sun X, et al. The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2006 Nov;180(1-2):126-34 [8]. Uehata M, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997 Oct 30;389(6654):990-4.

Chemical & Physical Properties

Boiling Point	506.2ºC at 760 mmHg
Melting Point	222 °C(dec.)
Molecular Formula	C₁₄H₁₈ClN₃O₂S
Molecular Weight	327.83
Flash Point	259.9ºC
PSA	70.68000
LogP	4.17030
InChIKey	LFVPBERIVUNMGV-UHFFFAOYSA-N
SMILES	Cl.O=S(=O)(c1cccc2cnccc12)N1CCCNCC1
Water Solubility	H2O: >200 mg/mL

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HM4033500

CHEMICAL NAME :: 1H-1,4-Diazepine, hexahydro-1-(5-isoquinolinylsulfonyl)-, monohydrochloride

CAS REGISTRY NUMBER :: 105628-07-7

LAST UPDATED :: 199612

DATA ITEMS CITED :: 12

MOLECULAR FORMULA :: C14-H17-N3-O2-S.Cl-H

MOLECULAR WEIGHT :: 327.86

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 335 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 20(Suppl 6),S1433,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 123 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 20(Suppl 6),S1433,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 59900 ug/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - convulsions or effect on seizure threshold Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 20(Suppl 6),S1433,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 274 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 20(Suppl 6),S1433,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 124 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 20(Suppl 6),S1433,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 67600 ug/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - convulsions or effect on seizure threshold Behavioral - Straub tail

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 20(Suppl 6),S1433,1992

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 20 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 26,740,1995 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 700 mg/kg/28D-C

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in bladder weight Blood - pigmented or nucleated red blood cells Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 20(Suppl 6),S1441,1992 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 2100 mg/kg

SEX/DURATION :: male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - other measures of fertility

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22,41,1994

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 440 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 20(Suppl 6),S1469,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 440 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - behavioral Reproductive - Effects on Newborn - physical

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 20(Suppl 6),S1469,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

DOSE :: 1 gm/kg

SEX/DURATION :: female 17-20 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22,61,1994

Safety Information

Hazard Codes	Xi
WGK Germany	3
RTECS	HM4031166
HS Code	2942000000

Customs

HS Code	2933990090
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Synonyms

5-(1,4-Diazepan-1-ylsulfonyl)isoquinoline hydrochloride (1:1)

Eril

5-((1,4-Diazepan-1-yl)sulfonyl)isoquinoline hydrochloride

MFCD00943198

Isoquinoline, 5-[(hexahydro-1H-1,4-diazepin-1-yl)sulfonyl]-, hydrochloride (1:1)

Fasudil HCl

Fasudil Monohydrochloride

1-(5-Isoquinolinesulfonyl)homopiperazine Hydrochloride

Fasudil Hydrochloride

5-(1-Homopiperazinyl)sulfonylisoquinoline Hydrochloride

Fasudil (Hydrochloride)

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