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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H27N3O3.2ClH
Molecular Weight 526.454
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NETARSUDIL DIHYDROCHLORIDE

SMILES

Cl.Cl.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=LDKTYVXXYUJVJM-FBHGDYMESA-N
InChI=1S/C28H27N3O3.2ClH/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);2*1H/t26-;;/m1../s1

HIDE SMILES / InChI

Description

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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
1.0 nM [Ki]
1.0 nM [Ki]
4.2 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Rhopressa
Primary
Rhopressa

Cmax

ValueDoseCo-administeredAnalytePopulation
1.51 ng/mL
0.53 mg/kg 1 times / day multiple, intravenous
NETARSUDIL METABOLITE AR-13503 unknown
Canis lupus

AUC

ValueDoseCo-administeredAnalytePopulation
3004 ng × h/mL
12.5 mg/kg single, intravenous
NETARSUDIL METABOLITE AR-13503 plasma
Canis lupus

T1/2

ValueDoseCo-administeredAnalytePopulation
19.5 h
unknown, unknown
NETARSUDIL METABOLITE AR-13503 plasma
Oryctolagus cuniculus

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as victim

PubMed

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
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.