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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H27N3O3.2CH4O3S
Molecular Weight 645.744
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NETARSUDIL MESYLATE

SMILES

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

InChI

InChIKey=QQDRLKRHJOAQDC-FBHGDYMESA-N
InChI=1S/C28H27N3O3.2CH4O3S/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;2*1-5(2,3)4/h3-14,16,26H,15,17,29H2,1-2H3,(H,31,32);2*1H3,(H,2,3,4)/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

Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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 Dec 16 01:58:08 UTC 2023
Edited
by admin
on Sat Dec 16 01:58:08 UTC 2023
Record UNII
VL756B1K0U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NETARSUDIL MESYLATE
USAN  
USAN  
Official Name English
ROCKLATAN COMPONENT NETARSUDIL DIMESYLATE
Common Name English
NETARSUDIL MESYLATE [USAN]
Common Name English
NETARSUDIL DIMESYLATE
Common Name English
BENZOIC ACID, 2,4-DIMETHYL-, (4-((1S)-1-(AMINOMETHYL)-2-(6-ISOQUINOLINYLAMINO)-2-OXOETHYL)PHENYL)METHYL ESTER, METHANESULFONATE (1:2)
Systematic Name English
AR-13324
Code English
Netarsudil mesilate [WHO-DD]
Common Name English
NETARSUDIL MESILATE
WHO-DD  
Common Name English
NETARSUDIL MESYLATE [ORANGE BOOK]
Common Name English
NETARSUDIL DIMESYLATE COMPONENT OF ROCKLATAN
Common Name English
NETARSUDIL DIMESYLATE [ORANGE BOOK]
Common Name English
(4-((1S)-1-(AMINOMETHYL)-2-(ISOQUINOLIN-6-YLAMINO)-2-OXOETHYL)PHENYL)METHYL 2,4-DIMETHYLBENZOATE, DIMETHANESULFONATE
Systematic Name English
RHOPRESSA
Brand Name English
NETARSUDIL DIMESYLATE [MI]
Common Name English
Code System Code Type Description
USAN
BC-103
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
CAS
1422144-42-0
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
ChEMBL
CHEMBL3545127
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
NCI_THESAURUS
C170214
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
MERCK INDEX
m12058
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
DAILYMED
VL756B1K0U
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
DRUG BANK
DBSALT002599
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
SMS_ID
100000174705
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
FDA UNII
VL756B1K0U
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
RXCUI
1992863
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
EPA CompTox
DTXSID301027773
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
PUBCHEM
90410375
Created by admin on Sat Dec 16 01:58:08 UTC 2023 , Edited by admin on Sat Dec 16 01:58:08 UTC 2023
PRIMARY
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