Ripasudil

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H18FN3O2S
Molecular Weight	323.386
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1CNCCCN1S(=O)(=O)C2=CC=CC3=CN=CC(F)=C23

InChI

InChIKey=QSKQVZWVLOIIEV-NSHDSACASA-N

InChI=1S/C15H18FN3O2S/c1-11-8-17-6-3-7-19(11)22(20,21)14-5-2-4-12-9-18-10-13(16)15(12)14/h2,4-5,9-11,17H,3,6-8H2,1H3/t11-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C15H18FN3O2S
Molecular Weight	323.386
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24502505
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25414122 | http://dwti.co.jp/english/business-outline/product-pipeline/glanatec

Ripasudil (K-115) is a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor. This compound, which was originally discovered by D. Western Therapeutics Institute, Inc., reduces intraocular pressure (IOP) by directly acting on the trabecular meshwork, thereby increasing conventional outflow through the Schlemm's canal. As a result of this mechanism of action, ripasudil may offer additive effects in the treatment of glaucoma and ocular hypertension when used in combination with agents such as prostaglandin analogues (which increase uveoscleral outflow) and β blockers (which reduce aqueous production). GLANATEC® (Ripasudil hydrochloride hydrate) ophthalmic solution 0.4% is launched in Japan for the treatment of glaucoma and ocular hypertension.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Rho-associated protein kinase 1 20 Target ID: CHEMBL3231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24502505	Inhibitor 8504		51.0 nM [IC50]
Rho-associated protein kinase 2 25 Target ID: CHEMBL2973 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24502505	Inhibitor 8504		19.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Glaucoma 57 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25414122	Primary		Approved 8583	GLANATEC Approved Use GLANATEC® (Ripasudil hydrochloride hydrate) ophthalmic solution 0.4% inhibits Rho kinase and promotes drainage of aqueous humor from main outflow. It consequently decreases intraocular pressure. It is usually used to treat glaucoma and ocular hypertension when other medicines for glaucoma have insufficient effect or can not be used. Launch Date 2014
Ocular hypertension 52 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25414122	Primary		Approved 8583	GLANATEC Approved Use GLANATEC® (Ripasudil hydrochloride hydrate) ophthalmic solution 0.4% inhibits Rho kinase and promotes drainage of aqueous humor from main outflow. It consequently decreases intraocular pressure. It is usually used to treat glaucoma and ocular hypertension when other medicines for glaucoma have insufficient effect or can not be used. Launch Date 2014

C_max

Value	Dose	Analyte	Population
0.115 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	72 μg single, ocular dose: 72 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.453 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	144 μg single, ocular dose: 144 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.656 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	288 μg single, ocular dose: 288 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.88 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	576 μg single, ocular dose: 576 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
0.018 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	72 μg single, ocular dose: 72 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.168 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	144 μg single, ocular dose: 144 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.39 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	288 μg single, ocular dose: 288 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.471 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	576 μg single, ocular dose: 576 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
0.728 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	144 μg single, ocular dose: 144 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.621 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	288 μg single, ocular dose: 288 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.659 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26678038	576 μg single, ocular dose: 576 μg route of administration: Ocular experiment type: SINGLE co-administered:	RIPASUDIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.8 % 2 times / day multiple, topical Highest studied dose Dose: 0.8 %, 2 times / day Route: topical Route: multiple Dose: 0.8 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	Other AEs: Conjunctival hyperemia, ALT increased... Other AEs: Conjunctival hyperemia (100%) ALT increased (12.5%) Hematocrit decreased (12.5%) Hemoglobin decreased (12.5%) Red blood cell count decreased (12.5%) White blood cell count increased (12.5%) ALP increased (12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
0.8 % single, topical Highest studied dose Dose: 0.8 % Route: topical Route: single Dose: 0.8 % Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	Other AEs: Conjunctival hyperemia, Creatine phosphokinase increased... Other AEs: Conjunctival hyperemia (87.5%) Creatine phosphokinase increased (25%) Triglycerides increased (12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
0.4 % 2 times / day multiple, topical Recommended Dose: 0.4 %, 2 times / day Route: topical Route: multiple Dose: 0.4 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33866572/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/33866572/	Disc. AE: Erythema... AEs leading to discontinuation/dose reduction: Erythema Sources: https://pubmed.ncbi.nlm.nih.gov/33866572/

AEs

AE	Significance	Dose	Population
Conjunctival hyperemia	100%	0.8 % 2 times / day multiple, topical Highest studied dose Dose: 0.8 %, 2 times / day Route: topical Route: multiple Dose: 0.8 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
ALP increased	12.5%	0.8 % 2 times / day multiple, topical Highest studied dose Dose: 0.8 %, 2 times / day Route: topical Route: multiple Dose: 0.8 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
ALT increased	12.5%	0.8 % 2 times / day multiple, topical Highest studied dose Dose: 0.8 %, 2 times / day Route: topical Route: multiple Dose: 0.8 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
Hematocrit decreased	12.5%	0.8 % 2 times / day multiple, topical Highest studied dose Dose: 0.8 %, 2 times / day Route: topical Route: multiple Dose: 0.8 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
Hemoglobin decreased	12.5%	0.8 % 2 times / day multiple, topical Highest studied dose Dose: 0.8 %, 2 times / day Route: topical Route: multiple Dose: 0.8 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
Red blood cell count decreased	12.5%	0.8 % 2 times / day multiple, topical Highest studied dose Dose: 0.8 %, 2 times / day Route: topical Route: multiple Dose: 0.8 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
White blood cell count increased	12.5%	0.8 % 2 times / day multiple, topical Highest studied dose Dose: 0.8 %, 2 times / day Route: topical Route: multiple Dose: 0.8 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
Triglycerides increased	12.5%	0.8 % single, topical Highest studied dose Dose: 0.8 % Route: topical Route: single Dose: 0.8 % Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
Creatine phosphokinase increased	25%	0.8 % single, topical Highest studied dose Dose: 0.8 % Route: topical Route: single Dose: 0.8 % Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
Conjunctival hyperemia	87.5%	0.8 % single, topical Highest studied dose Dose: 0.8 % Route: topical Route: single Dose: 0.8 % Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23787820/
Erythema	Disc. AE	0.4 % 2 times / day multiple, topical Recommended Dose: 0.4 %, 2 times / day Route: topical Route: multiple Dose: 0.4 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/33866572/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/33866572/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087	inhibitor 2438 substrate 1193	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057 CYP3A4/5 296 CYP2C8 1057	CYP3A5 446 CYP1A2 1197 CYP2C19 1119 CYP2B6 776	CYP2B6 669 CYP1A2 832

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 34.0	no [IC50 >25 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 34.0	no [IC50 >25 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 34.0	no [IC50 >25 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 34.0	no [IC50 >25 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_A100_1.pdf Page: 27.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_A100_1.pdf Page: 27.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_A100_1.pdf Page: 27.0	no
CYP3A4/5 357	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 34.0	yes [IC50 14 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 34.0	yes [IC50 3.8 uM]

Drug as victim

Target	Modality	Activity
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26678038/	minor
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26678038/	minor
CYP1A2 1197	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 22.0	no
CYP2B6 776	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 22.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 22.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 22.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_I103_1.pdf Page: 22.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.pmda.go.jp/drugs/2014/P201400129/270072000_22600AMX01307_A100_1.pdf Page: 9.0

PubMed

Title	Date	PubMed
Efficacy and safety of adding ripasudil to existing treatment regimens for reducing intraocular pressure.	2018-02	28063100
Efficacy of Ripasudil as a Second-line Medication in Addition to a Prostaglandin Analog in Patients with Exfoliation Glaucoma: A Pilot Study.	2017-06	28349329
Time Course of Conjunctival Hyperemia Induced by a Rho-kinase Inhibitor Anti-glaucoma Eye Drop: Ripasudil 0.4.	2017-05	27911106
Efficacy of the Additional Use of Ripasudil, a Rho-Kinase Inhibitor, in Patients With Glaucoma Inadequately Controlled Under Maximum Medical Therapy.	2017-02	27661993
Ocular hypotensive effects of a Rho-associated protein kinase inhibitor in rabbits.	2017	28408797
Ocular Penetration and Pharmacokinetics of Ripasudil Following Topical Administration to Rabbits.	2016-09	27463221
Vascular Normalization by ROCK Inhibitor: Therapeutic Potential of Ripasudil (K-115) Eye Drop in Retinal Angiogenesis and Hypoxia.	2016-04-01	27124322
Ripasudil: first global approval.	2014-12	25414122
Effects of K-115, a rho-kinase inhibitor, on aqueous humor dynamics in rabbits.	2014-08	24502505

Patents

Sample Use Guides

In Vivo Use Guide

GLANATEC® (Ripasudil hydrochloride hydrate) ophthalmic solution 0.4% one drop twice daily

Route of Administration: Topical

In Vitro Use Guide

Ripasudil but not fasudil significantly reduced VEGF-induced MYPT-1 phosphorylation in human retinal microvascular endothelial cells (HRMECs) at 30 μmol/L. Ripasudil significantly inhibited VEGF-induced HRMECs migration and proliferation.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 23:24:08 GMT 2025` Edited by `admin` on `Mon Mar 31 23:24:08 GMT 2025`
Record UNII	11978226XX
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ripasudil [INN]

Preferred Name

English

Ripasudil

Official Name

English

K-115 anhydrous free base

Systematic Name

English

1H-1,4-Diazepine, 1-[(4-fluoro-5-isoquinolinyl)sulfonyl]hexahydro-2-methyl-, (2S)-

Systematic Name

English

Isoquinoline, 4-fluoro-5-[[(2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl]sulfonyl]-

Systematic Name

English

RIPASUDIL [USAN]

Common Name

English

K-321 anhydrous free base

Code

English

Ripasudil [WHO-DD]

Common Name

English

4-Fluoro-5-[[(2S)-hexahydro-2-methyl-1H-1,4-diazepin-1-yl]sulfonyl]isoquinoline

Systematic Name

English

RIPASUDIL [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1404