Ripasudil

Summary

Ripasudil (CHEMBL3426621) is a phase-3 clinical-stage small molecule (ATC S01EX07) targeting PRKACA, ROCK1, and ROCK2; indicated across 5 conditions including fuchs’ endothelial dystrophy and corneal edema.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: S01EX07
• Targets: 3 (PRKACA, ROCK1, ROCK2)
• Indications: 5 conditions
• Clinical trials: 9
• Chemistry: 323.4 Da · C15H18FN3O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3426621
Name	Ripasudil
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	9863672
ATC	S01EX07
Molecular formula	C15H18FN3O2S
Molecular weight	323.4
InChIKey	QSKQVZWVLOIIEV-NSHDSACASA-N

SMILES: C[C@H]1CNCCCN1S(=O)(=O)C2=CC=CC3=CN=CC(=C32)F

IUPAC name: 4-fluoro-5-[[(2S)-2-methyl-1,4-diazepan-1-yl]sulfonyl]isoquinoline

Also known as: Ripasudil, ripasudil, RIPASUDIL

Parent form; salt/anhydrous children: CHEMBL4594454, CHEMBL6147188

Patent coverage: 387 distinct patent families (870 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 746 (86%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PRKACA	protein kinase, cAMP-dependent, catalytic, alpha subunit	Inhibition	5.68	2.9%	P17612
ROCK1	Rho associated coiled-coil containing protein kinase 1	Inhibition	7.29	1.4%	Q13464
ROCK2	Rho associated coiled-coil containing protein kinase 2	Inhibition	7.72	1.1%	O75116

Broader ChEMBL bioactivity targets: 17 (assay-derived). Sample: Dual specificity mitogen-activated protein kinase kinase 3, Aurora kinase B, 5’-AMP-activated protein kinase subunit gamma-1, Rho-associated protein kinase 2, Protein kinase C delta type, Serine/threonine-protein kinase N2, Cyclin-dependent kinase 9, Rho-associated protein kinase 1, Serine/threonine-protein kinase N1, Serine/threonine-protein kinase PLK4.

Bioactivity

ChEMBL activities: 31 potent at pChembl ≥ 5 of 34 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ROCK2	8.42	IC50	3.8	nM	CHEMBL_ACT_15246147
ROCK2	7.88	IC50	13.1	nM	CHEMBL_ACT_26124624
ROCK1	7.76	IC50	17.4	nM	CHEMBL_ACT_26124614
ROCK2	7.72	IC50	19	nM	CHEMBL_ACT_16493395
ROCK2	7.72	IC50	19	nM	CHEMBL_ACT_20681610
ROCK2	7.72	IC50	19	nM	CHEMBL_ACT_22396437
ROCK2	7.72	IC50	19	nM	CHEMBL_ACT_24861815
ROCK2	7.72	IC50	19	nM	CHEMBL_ACT_25033851
ROCK2	7.7	IC50	20	nM	CHEMBL_ACT_22401858
ROCK1	7.48	Kd	33	nM	CHEMBL_ACT_17935958
ROCK1	7.3	IC50	50	nM	CHEMBL_ACT_22401862
ROCK1	7.29	IC50	51	nM	CHEMBL_ACT_16493394
ROCK1	7.29	IC50	51	nM	CHEMBL_ACT_20681611
ROCK1	7.29	IC50	51	nM	CHEMBL_ACT_22396438
ROCK1	7.29	IC50	51	nM	CHEMBL_ACT_24861807
ROCK1	7.29	IC50	51	nM	CHEMBL_ACT_25033850
ROCK2	7.08	Kd	83	nM	CHEMBL_ACT_17936193
ROCK2	6.71	IC50	197	nM	CHEMBL_ACT_15246108
PKN2	6.54	Kd	285	nM	CHEMBL_ACT_17927559
ROCK2	6.48	Ki	330	nM	CHEMBL_ACT_24861823
PKN1	6.38	Kd	416	nM	CHEMBL_ACT_17927276
AURKB	5.94	Kd	1152	nM	CHEMBL_ACT_17884360
PRKAG1	5.74	Kd	1807	nM	CHEMBL_ACT_17929231
PRKCD	5.61	Kd	2470	nM	CHEMBL_ACT_17930339
MAP2K3	5.51	Kd	3079	nM	CHEMBL_ACT_17910903
MAP4K3	5.49	Kd	3219	nM	CHEMBL_ACT_17913829
PRKAA1	5.49	Kd	3269	nM	CHEMBL_ACT_17928254
NQO2	5.43	Kd	3699	nM	CHEMBL_ACT_17922328
PRKD2	5.43	Kd	3703	nM	CHEMBL_ACT_17931407
MARK2	5.22	Kd	6017	nM	CHEMBL_ACT_17917282

Target pathways

Aggregated over 3 target gene(s): PRKACA, ROCK1, ROCK2.

Top Reactome pathways

140 total, by targets touching each:

Pathway	Targets	Genes
Developmental Biology	3	PRKACA, ROCK1, ROCK2
Signal Transduction	3	PRKACA, ROCK1, ROCK2
Disease	3	PRKACA, ROCK1, ROCK2
Signaling by VEGF	3	PRKACA, ROCK1, ROCK2
Signaling by GPCR	3	PRKACA, ROCK1, ROCK2
GPCR downstream signalling	3	PRKACA, ROCK1, ROCK2
Axon guidance	3	PRKACA, ROCK1, ROCK2
VEGFA-VEGFR2 Pathway	3	PRKACA, ROCK1, ROCK2
Infectious disease	3	PRKACA, ROCK1, ROCK2
Signaling by Receptor Tyrosine Kinases	3	PRKACA, ROCK1, ROCK2
Nervous system development	3	PRKACA, ROCK1, ROCK2
Innate Immune System	2	PRKACA, ROCK1
Immune System	2	PRKACA, ROCK1
Signaling by Rho GTPases	2	ROCK1, ROCK2
RHO GTPase Effectors	2	ROCK1, ROCK2
EPH-Ephrin signaling	2	ROCK1, ROCK2
Semaphorin interactions	2	ROCK1, ROCK2
EPHB-mediated forward signaling	2	ROCK1, ROCK2
EPHA-mediated growth cone collapse	2	ROCK1, ROCK2
Sema4D in semaphorin signaling	2	ROCK1, ROCK2
G alpha (12/13) signalling events	2	ROCK1, ROCK2
Sema4D induced cell migration and growth-cone collapse	2	ROCK1, ROCK2
RHO GTPases Activate ROCKs	2	ROCK1, ROCK2
RHOA GTPase cycle	2	ROCK1, ROCK2
RHO GTPase cycle	2	ROCK1, ROCK2
RHOB GTPase cycle	2	ROCK1, ROCK2
RHOC GTPase cycle	2	ROCK1, ROCK2
RHOH GTPase cycle	2	ROCK1, ROCK2
RHOBTB1 GTPase cycle	2	ROCK1, ROCK2
Potential therapeutics for SARS	2	ROCK1, ROCK2

Dominant GO biological processes

GO term	Targets
protein phosphorylation	3
regulation of microtubule cytoskeleton organization	2
peptidyl-serine phosphorylation	2
mitotic cytokinesis	2
epithelial to mesenchymal transition	2
aortic valve morphogenesis	2
smooth muscle contraction	2
signal transduction	2
Rho protein signal transduction	2
positive regulation of cardiac muscle hypertrophy	2
positive regulation of gene expression	2
negative regulation of angiogenesis	2
actin cytoskeleton organization	2
regulation of cell adhesion	2
cortical actin cytoskeleton organization	2

Indications & clinical

Indications

5 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
Fuchs’ endothelial dystrophy	3	MONDO:0005321	Orphanet:98974
corneal edema	3	MONDO:0006712	EFO:1000879
glaucoma	3	MONDO:0005041	MONDO:0005041
retinopathy of prematurity	1	MONDO:0006952	EFO:1001158

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE3	7
PHASE4	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03249337	PHASE4	RECRUITING	Glanatec(R) for Descemet Stripping in Fuch’s Endothelial Dystrophy
NCT05275972	PHASE3	RECRUITING	Descemet Endothelial Thickness Comparison Trial II
NCT05289661	PHASE3	ACTIVE_NOT_RECRUITING	Descemet Endothelial Thickness Comparison Trial I
NCT06048380	PHASE3	RECRUITING	The Effects of Ripasudil in Patients With FED Undergoing Femtosecond Laser Assisted Cataract Surgery
NCT04620135	PHASE3	COMPLETED	Efficacy and Safety Study of Netarsudil 0.02% Ophthalmic Solution Compared to Ripasudil Hydrochloride Hydrate 0.4% Ophthalmic Solution in Japanese Subjects With Primary Open Angle Glaucoma or Ocular Hypertension
NCT05528172	PHASE3	COMPLETED	A Study to Investigate the Safety and Efficacy of Ripasudil (K-321) Eye Drops After Cataract Surgery
NCT05795699	PHASE3	COMPLETED	A Study to Evaluate the Safety and Efficacy of K-321 Eye Drops After Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD)
NCT05826353	PHASE3	COMPLETED	A Study to Investigate the Safety and Efficacy of K-321 Eye Drops After Simultaneous Cataract Surgery and Descemetorhexis in Participants With Fuchs Endothelial Corneal Dystrophy (FECD)
NCT05636579	PHASE1	RECRUITING	Study to Assess Safety and Tolerability of Multiple Doses of EO2002

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

59 molecules share ≥1 primary target. Top 59 by shared-target count:

Molecule	Source	Status	Shared targets
belumosudil	ChEMBL + PubChem	Phase 4 (approved)	PRKACA, ROCK1, ROCK2
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	PRKACA, ROCK1, ROCK2
BARICITINIB	ChEMBL	Phase 4 (approved)	PRKACA, ROCK1, ROCK2
CAPIVASERTIB	ChEMBL	Phase 4 (approved)	PRKACA, ROCK1, ROCK2
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	PRKACA, ROCK1, ROCK2
AFURESERTIB	ChEMBL	Phase 3	PRKACA, ROCK1, ROCK2
FASUDIL	ChEMBL	Phase 3	PRKACA, ROCK1, ROCK2
LESTAURTINIB	ChEMBL	Phase 3	PRKACA, ROCK1, ROCK2
LINIFANIB	ChEMBL	Phase 3	PRKACA, ROCK1, ROCK2
CENISERTIB	ChEMBL	Phase 2	PRKACA, ROCK1, ROCK2
R-406	ChEMBL	Phase 2	PRKACA, ROCK1, ROCK2
SAR-407899 FREE BASE	ChEMBL	Phase 2	PRKACA, ROCK1, ROCK2
UCN-01	ChEMBL	Phase 2	PRKACA, ROCK1, ROCK2
UPROSERTIB	ChEMBL	Phase 2	PRKACA, ROCK1, ROCK2
Afatinib	PubChem	Approved	PRKACA, ROCK1, ROCK2
Binimetinib	PubChem	Approved	PRKACA, ROCK1, ROCK2
dacomitinib	PubChem	Approved	PRKACA, ROCK1, ROCK2
Fostamatinib	PubChem	Approved	PRKACA, ROCK1, ROCK2
Gefitinib	PubChem	Approved	PRKACA, ROCK1, ROCK2
Idelalisib	PubChem	Approved	PRKACA, ROCK1, ROCK2
Pazopanib	PubChem	Approved	PRKACA, ROCK1, ROCK2
regorafenib	PubChem	Approved	PRKACA, ROCK1, ROCK2
Selumetinib	PubChem	Approved	PRKACA, ROCK1, ROCK2
Trametinib	PubChem	Approved	PRKACA, ROCK1, ROCK2
BOSUTINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
FEDRATINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
MOMELOTINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
NETARSUDIL	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
RUXOLITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
SUNITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
TOFACITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
UPADACITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
ALVOCIDIB	ChEMBL	Phase 3	ROCK1, ROCK2
DOVITINIB	ChEMBL	Phase 3	ROCK1, ROCK2
BMS-690514	ChEMBL	Phase 2	PRKACA, ROCK1
DECERNOTINIB	ChEMBL	Phase 2	ROCK1, ROCK2
ILORASERTIB	ChEMBL	Phase 2	ROCK1, ROCK2
LAUROGUADINE	ChEMBL	Phase 2	ROCK1, ROCK2
RG-547	ChEMBL	Phase 2	ROCK1, ROCK2
SU-014813	ChEMBL	Phase 2	ROCK1, ROCK2
VEROSUDIL	ChEMBL	Phase 2	ROCK1, ROCK2
ZOTIRACICLIB	ChEMBL	Phase 2	ROCK1, ROCK2
CERITINIB	ChEMBL	Phase 4 (approved)	ROCK2
PALBOCICLIB	ChEMBL	Phase 4 (approved)	ROCK2
PONATINIB	ChEMBL	Phase 4 (approved)	PRKACA
VANDETANIB	ChEMBL	Phase 4 (approved)	ROCK2
ALISERTIB	ChEMBL	Phase 3	PRKACA
ENZASTAURIN	ChEMBL	Phase 3	PRKACA
RUBOXISTAURIN	ChEMBL	Phase 3	PRKACA
AT-9283	ChEMBL	Phase 2	PRKACA
BMS-754807	ChEMBL	Phase 2	PRKACA
BMS-777607	ChEMBL	Phase 2	PRKACA
ELLAGIC ACID	ChEMBL	Phase 2	PRKACA
FORETINIB	ChEMBL	Phase 2	ROCK2
PH-797804	ChEMBL	Phase 2	ROCK2
SIMUROSERTIB	ChEMBL	Phase 2	ROCK1
VX-702	ChEMBL	Phase 2	ROCK1
Belzutifan	PubChem	Approved	ROCK2
Imatinib	PubChem	Approved	PRKACA