U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C28H27N3O3
Molecular Weight 453.5333
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NETARSUDIL

SMILES

Cc1ccc(c(C)c1)C(=O)OCc2ccc(cc2)[C@@]([H])(CN)C(=O)Nc3ccc4cnccc4c3

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 453.5333
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Netarsudil ophthalmic solution (Rhopressa) is a Rho kinase inhibitor for the treatment of open-angle glaucoma or ocular hypertension. As of December 18, 2017 the FDA approved Aerie Pharmaceutical's Rhopressa (netarsudil ophthalmic solution) 0.02% for the indication of reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Acting as both a rho kinase inhibitor and a norepinephrine transport inhibitor, Netarsudil is a novel glaucoma medication in that it specifically targets the conventional trabecular pathway of aqueous humour outflow to act as an inhibitor to the rho kinase and norepinephrine transporters found there as opposed to affecting protaglandin F2-alpha analog like mechanisms in the unconventional uveoscleral pathway that many other glaucoma medications demonstrate.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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

1.51346885E12
Primary
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

1.51346885E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.51 ng/mL
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
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
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: Page: 2
unhealthy, adult
Health Status: unhealthy
Condition: open-angle glaucoma or ocular hypertension
Age Group: adult
Sex: unknown
Sources: Page: 2
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: Page: 6.1
unhealthy, adult
Health Status: unhealthy
Condition: open-angle glaucoma or ocular hypertension
Age Group: adult
Sex: unknown
Sources: Page: 6.1
Other AEs: Conjunctival hyperemia, Eye disorders NEC...
Other AEs:
Conjunctival hyperemia (53%)
Eye disorders NEC (20%)
Ocular signs and symptoms NEC (5 - 10)
Sources: Page: 6.1
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: Page: 6.1
unhealthy, adult
Health Status: unhealthy
Condition: open-angle glaucoma or ocular hypertension
Age Group: adult
Sex: unknown
Sources: Page: 6.1
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: Page: 6.1
unhealthy, adult
Health Status: unhealthy
Condition: open-angle glaucoma or ocular hypertension
Age Group: adult
Sex: unknown
Sources: Page: 6.1
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: Page: 6.1
unhealthy, adult
Health Status: unhealthy
Condition: open-angle glaucoma or ocular hypertension
Age Group: adult
Sex: unknown
Sources: Page: 6.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
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

Sample Use Guides

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 Sat Jun 26 06:19:14 UTC 2021
Edited
by admin
on Sat Jun 26 06:19:14 UTC 2021
Record UNII
W6I5QDT7QI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NETARSUDIL
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
AR-11324 FREE BASE
Code English
NETARSUDIL [USAN]
Common Name English
NETARSUDIL [MI]
Common Name English
NETARSUDIL [INN]
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
NETARSUDIL [WHO-DD]
Common Name English
Classification Tree Code System Code
NDF-RT N0000193788
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
WHO-ATC S01EX05
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
Code System Code Type Description
DRUG CENTRAL
5269
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
CAS
1254032-66-0
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
FDA UNII
W6I5QDT7QI
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
RXCUI
1992864
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545127
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
PUBCHEM
66599893
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
LACTMED
Netarsudil
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
NCI_THESAURUS
C170213
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
MERCK INDEX
M12058
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
DRUG BANK
DB13931
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
INN
10160
Created by admin on Sat Jun 26 06:19:15 UTC 2021 , Edited by admin on Sat Jun 26 06:19:15 UTC 2021
PRIMARY
Related Record Type Details
OFF-TARGET->INHIBITOR
IC50
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
TARGET -> INHIBITOR
Ki
BINDER->LIGAND
BINDING
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
Ki
Related Record Type Details
METABOLITE ACTIVE -> PARENT
5 times more active than NETARSUDIL
MAJOR
Related Record Type Details
ACTIVE MOIETY