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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H19N3O2
Molecular Weight 321.3731
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AR-13503

SMILES

NC[C@@H](C(=O)NC1=CC2=C(C=C1)C=NC=C2)C3=CC=C(CO)C=C3

InChI

InChIKey=LTXBFJFJUIJOQE-GOSISDBHSA-N
InChI=1S/C19H19N3O2/c20-10-18(14-3-1-13(12-23)2-4-14)19(24)22-17-6-5-16-11-21-8-7-15(16)9-17/h1-9,11,18,23H,10,12,20H2,(H,22,24)/t18-/m1/s1

HIDE SMILES / InChI

Molecular Formula C19H19N3O2
Molecular Weight 321.3731
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

2017
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

2017
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
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 Dec 16 14:07:31 GMT 2023
Edited
by admin
on Sat Dec 16 14:07:31 GMT 2023
Record UNII
4MVW7F3BCT
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AR-13503
Code English
NETARSUDIL METABOLITE AR-13503
Common Name English
BENZENEACETAMIDE, .ALPHA.-(AMINOMETHYL)-4-(HYDROXYMETHYL)-N-6-ISOQUINOLINYL-, (S)-
Systematic Name English
Code System Code Type Description
CAS
1254032-16-0
Created by admin on Sat Dec 16 14:07:32 GMT 2023 , Edited by admin on Sat Dec 16 14:07:32 GMT 2023
NON-SPECIFIC STEREOCHEMISTRY
FDA UNII
4MVW7F3BCT
Created by admin on Sat Dec 16 14:07:32 GMT 2023 , Edited by admin on Sat Dec 16 14:07:32 GMT 2023
PRIMARY
PUBCHEM
134128281
Created by admin on Sat Dec 16 14:07:32 GMT 2023 , Edited by admin on Sat Dec 16 14:07:32 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Ki
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
Ki
Related Record Type Details
PARENT -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY