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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H27N3O3
Molecular Weight 453.5323
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NETARSUDIL

SMILES

CC1=CC(C)=C(C=C1)C(=O)OCC2=CC=C(C=C2)[C@@H](CN)C(=O)NC3=CC=C4C=NC=CC4=C3

InChI

InChIKey=OURRXQUGYQRVML-AREMUKBSSA-N
InChI=1S/C28H27N3O3/c1-18-3-10-25(19(2)13-18)28(33)34-17-20-4-6-21(7-5-20)26(15-29)27(32)31-24-9-8-23-16-30-12-11-22(23)14-24/h3-14,16,26H,15,17,29H2,1-2H3,(H,31,32)/t26-/m1/s1

HIDE SMILES / InChI
Molecular Formula C28H27N3O3
Molecular Weight 453.5323
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

AR-13503 is an active metabolite of Netarsudil

Originator

Approval Year

2017
411
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 1.0 nM [Ki]
Inhibitor
8504
 1.0 nM [Ki]
Inhibitor
8504
Inhibitor
8504
Inhibitor
8504
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
Rhopressa

Approved Use

RHOPRESSA® (netarsudil ophthalmic solution) 0.02% is a Rho kinase inhibitor indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

Launch Date

2017
Primary
Approved
8583
Rhopressa

Approved Use

RHOPRESSA® (netarsudil ophthalmic solution) 0.02% is a Rho kinase inhibitor indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

Launch Date

2017
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.51 ng/mL
DRUG LABEL
https://www.ema.europa.eu/en/documents/assessment-report/rhokiinsa-epar-public-assessment-report_en.pdf
0.53 mg/kg 1 times / day multiple, intravenous
dose: 0.53 mg/kg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
NETARSUDIL METABOLITE AR-13503 unknown
Canis lupus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3004 ng × h/mL
DRUG LABEL
https://www.ema.europa.eu/en/documents/assessment-report/rhokiinsa-epar-public-assessment-report_en.pdf
12.5 mg/kg single, intravenous
dose: 12.5 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NETARSUDIL METABOLITE AR-13503 plasma
Canis lupus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
19.5 h
DRUG LABEL
https://www.ema.europa.eu/en/documents/assessment-report/rhokiinsa-epar-public-assessment-report_en.pdf
unknown, unknown
 NETARSUDIL METABOLITE AR-13503 plasma
Oryctolagus cuniculus
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
0.02 % 2 times / day multiple, ophthalmic
Highest studied dose
Dose: 0.02 %, 2 times / day
Route: ophthalmic
Route: multiple
Dose: 0.02 %, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
0.02 % 1 times / day multiple, ophthalmic
Recommended
Dose: 0.02 %, 1 times / day
Route: ophthalmic
Route: multiple
Dose: 0.02 %, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
Other AEs: Conjunctival hyperemia, Eye disorders NEC...
Other AEs:
Conjunctival hyperemia (53%)
Eye disorders NEC (20%)
Ocular signs and symptoms NEC (5 - 10)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Eye disorders NEC 20%
0.02 % 1 times / day multiple, ophthalmic
Recommended
Dose: 0.02 %, 1 times / day
Route: ophthalmic
Route: multiple
Dose: 0.02 %, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
Ocular signs and symptoms NEC 5 - 10
0.02 % 1 times / day multiple, ophthalmic
Recommended
Dose: 0.02 %, 1 times / day
Route: ophthalmic
Route: multiple
Dose: 0.02 %, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
Conjunctival hyperemia 53%
0.02 % 1 times / day multiple, ophthalmic
Recommended
Dose: 0.02 %, 1 times / day
Route: ophthalmic
Route: multiple
Dose: 0.02 %, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2507

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2C19
2057
CYP
303
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
2141
 yes [Inhibition 10 uM]
CYP2D6
2546
 yes [Inhibition 10 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP
303
 no
Sourcing

Sourcing

Vendor/AggregatorIDURL
AA Blocks
AA01FHG7
https://www.aablocks.com/goods/Goods/detail?id=AA01FHG7
Chem Scene
CS-0043468
http://www.chemscene.com/CS-0043468.html
Chemspace
CSSS00159268835
https://chem-space.com/CSSS00159268835
CSNpharm
CSN21168
https://www.csnpharm.com/products/ar-13324-m1-metabolite.html
MedChem Express
HY-12798C
https://www.medchemexpress.com/AR-13324_M1_metabolite.html
MolPort
MolPort-046-418-075
Smolecule
S519222
http://www.smolecule.com/products/s519222
THE BioTek
bt-259783
https://www.thebiotek.com/product/inhibitors/bt-259783
ZINC
ZINC000113146450
http://zinc15.docking.org/substances/ZINC000113146450
PubMed

PubMed

TitleDatePubMed
Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms.
2016 Nov 1
Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes.
2016 Sep 15
Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2).
2018 Feb
Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma.
2018 Jan/Feb
Patents

Patents

CN107434780A
4
US2017204065
4
US9415043
4

Sample Use Guides

In Vivo Use Guide
RHOPRESSA® (netarsudil ophthalmic solution) 0.02%, for topical ophthalmic use. One drop into the affected eye(s) once daily in the evening.
Route of Administration: Topical
In Vitro Use Guide
Curator's Comment: At 10 uM, Netarsudil (AR-13324) inhibits NET by 96% and SERT by 94%. In a kinase screening panel 0.5 uM AR-13324 inhibited 11 kinases by >90%. https://www.ncbi.nlm.nih.gov/pubmed/27072905
Netarsudil inhibited kinases ROCK1 and ROCK2 with a Ki of 1 nM each, disrupted actin stress fibers and focal adhesions in TM cells with IC50s of 79 and 16 nM, respectively, and blocked the profibrotic effects of TGF-β2 in HTM cells.
Substance Class Chemical
Created
by admin
on Mon Mar 31 20:50:40 GMT 2025
Edited
by admin
on Mon Mar 31 20:50:40 GMT 2025
Record UNII
W6I5QDT7QI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NETARSUDIL
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
netarsudil [INN]
Preferred Name English
AR-11324 FREE BASE
Code English
NETARSUDIL [USAN]
Common Name English
Netarsudil [WHO-DD]
Common Name English
NETARSUDIL [MI]
Common Name English
(4-((1S)-1-(AMINOMETHYL)-2-(ISOQUINOLIN-6-YLAMINO)-2-OXOETHYL)PHENYL)METHYL 2,4- DIMETHYLBENZOATE
Systematic Name English
BENZOIC ACID, 2,4-DIMETHYL-, (4-((1S)-1-(AMINOMETHYL)-2-(6-ISOQUINOLINYLAMINO)-2-OXOETHYL)PHENYL)METHYL ESTER
Common Name English
Classification Tree Code System Code
NDF-RT N0000193788
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
WHO-ATC S01EX05
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
Code System Code Type Description
DRUG CENTRAL
5269
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
CAS
1254032-66-0
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
DAILYMED
W6I5QDT7QI
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
EPA CompTox
DTXSID001027774
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
FDA UNII
W6I5QDT7QI
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
RXCUI
1992864
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
ChEMBL
CHEMBL3545127
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
PUBCHEM
66599893
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
USAN
BC-102
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
LACTMED
Netarsudil
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
NCI_THESAURUS
C170213
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
SMS_ID
100000174704
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
WIKIPEDIA
Netarsudil
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
MERCK INDEX
m12058
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
DRUG BANK
DB13931
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
INN
10160
Created by admin on Mon Mar 31 20:50:40 GMT 2025 , Edited by admin on Mon Mar 31 20:50:40 GMT 2025
PRIMARY
Related Record Type Details
POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY H MEMBER 2
OFF-TARGET->INHIBITOR
IC50
Structure of NETARSUDIL DIHYDROCHLORIDE
SALT/SOLVATE -> PARENT
SODIUM-DEPENDENT NORADRENALINE TRANSPORTER
TARGET -> INHIBITOR
RHO-ASSOCIATED PROTEIN KINASE 2
TARGET -> INHIBITOR
Ki
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Structure of Netarsudil Mesylate
SALT/SOLVATE -> PARENT
RHO-ASSOCIATED PROTEIN KINASE 1
TARGET -> INHIBITOR
Ki
Related Record Type Details
Structure of AR-13503
METABOLITE ACTIVE -> PARENT
MAJOR
Related Record Type Details
Structure of AR-13503
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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