Netarsudil

Summary

Netarsudil (CHEMBL4594250) is an approved small molecule (ATC S01EX05) targeting ROCK1 and ROCK2; indicated across 5 conditions including fuchs’ endothelial dystrophy and glaucoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: S01EX05
• Targets: 2 (ROCK1, ROCK2)
• Indications: 5 conditions
• Clinical trials: 22
• Chemistry: 453.5 Da · C28H27N3O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4594250
Name	Netarsudil
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	66599893
ATC	S01EX05
Molecular formula	C28H27N3O3
Molecular weight	453.5
InChIKey	OURRXQUGYQRVML-AREMUKBSSA-N

SMILES: CC1=CC(=C(C=C1)C(=O)OCC2=CC=C(C=C2)[C@@H](CN)C(=O)NC3=CC4=C(C=C3)C=NC=C4)C

IUPAC name: [4-[(2S)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 2,4-dimethylbenzoate

Also known as: AR-11324 FREE BASE, AR-13324, Netarsudil, NETARSUDIL, (S)-Netarsudil

Parent form; salt/anhydrous children: CHEMBL4594251, CHEMBL4796289

Patent coverage: 425 distinct patent families (1,025 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 893 (87%) 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
ROCK1	Rho associated coiled-coil containing protein kinase 1	Inhibition	7.49	1.4%	Q13464
ROCK2	Rho associated coiled-coil containing protein kinase 2	Inhibition	7.95	1.1%	O75116

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Rho-associated protein kinase 2, Rho-associated protein kinase 1.

Bioactivity

ChEMBL activities: 34 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
ROCK1	9	Ki	1	nM	CHEMBL_ACT_24861806
ROCK2	9	Ki	1	nM	CHEMBL_ACT_24861814
ROCK1	9	Ki	1	nM	CHEMBL_ACT_25033852
ROCK2	9	Ki	1	nM	CHEMBL_ACT_25033854
ROCK1	9	Ki	1	nM	CHEMBL_ACT_26023208
ROCK2	9	Ki	1	nM	CHEMBL_ACT_26023209
ROCK2	8.7	Ki	2	nM	CHEMBL_ACT_25033860
ROCK2	8.38	Ki	4.2	nM	CHEMBL_ACT_22396435
ROCK1	8.26	IC50	5.5	nM	CHEMBL_ACT_28967915
ROCK2	8.1	IC50	8	nM	CHEMBL_ACT_28840892
ROCK2	7.99	IC50	10.18	nM	CHEMBL_ACT_26124623
ROCK2	7.95	IC50	11.2	nM	CHEMBL_ACT_19072294
ROCK1	7.88	IC50	13.18	nM	CHEMBL_ACT_26124613
ROCK1	7.85	IC50	14	nM	CHEMBL_ACT_28840895
ROCK2	7.82	IC50	15	nM	CHEMBL_ACT_28840880
ROCK1	7.82	IC50	15	nM	CHEMBL_ACT_28840919
ROCK2	7.75	IC50	18	nM	CHEMBL_ACT_28840886
ROCK1	7.75	IC50	18	nM	CHEMBL_ACT_28840952
ROCK1	7.72	IC50	19	nM	CHEMBL_ACT_28840925
ROCK1	7.72	IC50	19	nM	CHEMBL_ACT_28840931
ROCK1	7.72	IC50	19	nM	CHEMBL_ACT_28840940
ROCK1	7.7	IC50	20	nM	CHEMBL_ACT_28840943
ROCK1	7.68	IC50	21	nM	CHEMBL_ACT_28840916
ROCK1	7.68	IC50	21	nM	CHEMBL_ACT_28840934
ROCK1	7.64	IC50	23	nM	CHEMBL_ACT_28840907
ROCK1	7.58	IC50	26	nM	CHEMBL_ACT_28840889
ROCK1	7.58	IC50	26	nM	CHEMBL_ACT_28840937
ROCK1	7.57	IC50	27	nM	CHEMBL_ACT_28840928
ROCK1	7.49	IC50	32.6	nM	CHEMBL_ACT_19072296
ROCK1	7.48	IC50	33	nM	CHEMBL_ACT_28840946

Target pathways

Aggregated over 2 target gene(s): ROCK1, ROCK2.

Top Reactome pathways

40 total, by targets touching each:

Pathway	Targets	Genes
Developmental Biology	2	ROCK1, ROCK2
Signal Transduction	2	ROCK1, ROCK2
Disease	2	ROCK1, ROCK2
Signaling by VEGF	2	ROCK1, ROCK2
Signaling by Rho GTPases	2	ROCK1, ROCK2
RHO GTPase Effectors	2	ROCK1, ROCK2
EPH-Ephrin signaling	2	ROCK1, ROCK2
Signaling by GPCR	2	ROCK1, ROCK2
Semaphorin interactions	2	ROCK1, ROCK2
GPCR downstream signalling	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
Axon guidance	2	ROCK1, ROCK2
VEGFA-VEGFR2 Pathway	2	ROCK1, ROCK2
RHO GTPases Activate ROCKs	2	ROCK1, ROCK2
Infectious disease	2	ROCK1, ROCK2
RHOA GTPase cycle	2	ROCK1, ROCK2
Signaling by Receptor Tyrosine Kinases	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
Nervous system development	2	ROCK1, ROCK2
Potential therapeutics for SARS	2	ROCK1, ROCK2
SARS-CoV Infections	2	ROCK1, ROCK2
RHOBTB GTPase Cycle	2	ROCK1, ROCK2

Dominant GO biological processes

GO term	Targets
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
actomyosin structure organization	2
regulation of actin cytoskeleton organization	2
positive regulation of MAPK cascade	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
glaucoma	3	MONDO:0005041	MONDO:0005041
corneal edema	2	MONDO:0006712	EFO:1000879
open-angle glaucoma	0	MONDO:0005338	EFO:0004190

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

Clinical trials

Total trials: 22.

Phase distribution

Phase	Trials
PHASE3	5
PHASE4	4
PHASE2	3
EARLY_PHASE1	3
Not specified	3
PHASE2/PHASE3	2
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07325240	PHASE4	RECRUITING	24-hour Effect of Rocklatan Compared With Latanoprost in Open Angle Glaucoma and Ocular Hypertension Patients
NCT04981886	PHASE4	UNKNOWN	Intraocular Pressure Reduction Efficacy of Rhopressa and Lumigan in Normal Tension Glaucoma
NCT05283395	PHASE4	COMPLETED	Rocklatan® Evaluation
NCT06449352	PHASE4	COMPLETED	Effect of Netarsudil vs Brimonidine in NTG Patients on Latanoprost
NCT05660447	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Multi-Center Study on the Use of Rho-Kinase Inhibitor to Reduce or Prevent PVR in RRD Eyes at High Risk for PVR
NCT02558400	PHASE3	COMPLETED	Double-masked Study of PG324 Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension
NCT02674854	PHASE3	COMPLETED	Double-masked Study of PG324 Ophthalmic Solution in Patients With Open-angle Glaucoma or Ocular Hypertension
NCT03248037	PHASE3	COMPLETED	Trial of Netarsudil for Prevention of Corticosteroid-induced Intraocular Pressure Elevation
NCT03284853	PHASE3	COMPLETED	Safety and Efficacy Study of PG324 (Netarsudil/Latanoprost 0.02% / 0.005%) Ophthalmic Solution Compared to GANFORT® Ophthalmic Solution in Open Angle Glaucoma or Ocular Hypertension
NCT03971357	PHASE2/PHASE3	TERMINATED	Trial of Netarsudil for Acceleration of Corneal Endothelial Restoration
NCT07082816	PHASE3	COMPLETED	Reformulated PG324 Ophthalmic Solution for Intraocular Pressure Reduction
NCT06033703	PHASE1/PHASE2	RECRUITING	Topical Netarsudil for the Prevention of Proliferative Vitreoretinopathy in Patients With Retinal Detachment
NCT02057575	PHASE2	COMPLETED	Study Assessing Safety and Efficacy of PG324 Ophthalmic Solution in Patients With Elevated Intraocular Pressure
NCT04498169	PHASE2	COMPLETED	A Phase 2 Study Evaluating the Safety and Efficacy of Netarsudil Ophthalmic Solution in Patients With Corneal Edema Due to Fuchs Corneal Dystrophy
NCT06441643	PHASE2	COMPLETED	Next Generation Rocklatan
NCT02406287	PHASE1	COMPLETED	A Controlled Study of the Aqueous Humor Dynamics of AR-13324 Ophthalmic Solution in Healthy Adult Volunteers
NCT04057053	EARLY_PHASE1	COMPLETED	Netarsudil Use After Descemetorhexis Without Endothelial Keratoplasty
NCT04234932	EARLY_PHASE1	UNKNOWN	Short-term Effect of Rho-kinase Inhibitor on Retinal Circulation
NCT04752020	EARLY_PHASE1	COMPLETED	Netarsudil Use After Descemtorhexis Without Endothelial Keratoplasty
NCT06960629	Not specified	ENROLLING_BY_INVITATION	The Effect of ROCK Inhibitors on Corneas of Patients With Glaucoma and Pseudophakic Bullous Keratopathy (PBK)
NCT06969586	Not specified	ENROLLING_BY_INVITATION	The Effect of Topical Rho-kinase Inhibitors on Corneas of Patients With Fuchs Endothelial Corneal Dystrophy
NCT04064918	Not specified	WITHDRAWN	Effects of Netarsudil and Timolol on Retinal Blood Vessel Density and Visual Acuity

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.

51 molecules share ≥1 primary target. Top 51 by shared-target count:

Molecule	Source	Status	Shared targets
BELUMOSUDIL	ChEMBL + PubChem	Phase 4 (approved)	ROCK1, ROCK2
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	ROCK1, ROCK2
BARICITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
BOSUTINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
CAPIVASERTIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
FEDRATINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
MOMELOTINIB	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
AFURESERTIB	ChEMBL	Phase 3	ROCK1, ROCK2
ALVOCIDIB	ChEMBL	Phase 3	ROCK1, ROCK2
DOVITINIB	ChEMBL	Phase 3	ROCK1, ROCK2
FASUDIL	ChEMBL	Phase 3	ROCK1, ROCK2
LESTAURTINIB	ChEMBL	Phase 3	ROCK1, ROCK2
LINIFANIB	ChEMBL	Phase 3	ROCK1, ROCK2
RIPASUDIL	ChEMBL	Phase 3	ROCK1, ROCK2
CENISERTIB	ChEMBL	Phase 2	ROCK1, ROCK2
DECERNOTINIB	ChEMBL	Phase 2	ROCK1, ROCK2
ILORASERTIB	ChEMBL	Phase 2	ROCK1, ROCK2
LAUROGUADINE	ChEMBL	Phase 2	ROCK1, ROCK2
R-406	ChEMBL	Phase 2	ROCK1, ROCK2
RG-547	ChEMBL	Phase 2	ROCK1, ROCK2
RIPASUDIL HYDROCHLORIDE DIHYDRATE	ChEMBL	Phase 2	ROCK1, ROCK2
SAR-407899 FREE BASE	ChEMBL	Phase 2	ROCK1, ROCK2
SU-014813	ChEMBL	Phase 2	ROCK1, ROCK2
UCN-01	ChEMBL	Phase 2	ROCK1, ROCK2
UPROSERTIB	ChEMBL	Phase 2	ROCK1, ROCK2
VEROSUDIL	ChEMBL	Phase 2	ROCK1, ROCK2
ZOTIRACICLIB	ChEMBL	Phase 2	ROCK1, ROCK2
Afatinib	PubChem	Approved	ROCK1, ROCK2
Binimetinib	PubChem	Approved	ROCK1, ROCK2
dacomitinib	PubChem	Approved	ROCK1, ROCK2
Fostamatinib	PubChem	Approved	ROCK1, ROCK2
Gefitinib	PubChem	Approved	ROCK1, ROCK2
Idelalisib	PubChem	Approved	ROCK1, ROCK2
Pazopanib	PubChem	Approved	ROCK1, ROCK2
regorafenib	PubChem	Approved	ROCK1, ROCK2
Selumetinib	PubChem	Approved	ROCK1, ROCK2
Trametinib	PubChem	Approved	ROCK1, ROCK2
CERITINIB	ChEMBL	Phase 4 (approved)	ROCK2
PALBOCICLIB	ChEMBL	Phase 4 (approved)	ROCK2
VANDETANIB	ChEMBL	Phase 4 (approved)	ROCK2
BMS-690514	ChEMBL	Phase 2	ROCK1
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