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
SMILES
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=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
| 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 |
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
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 1.0 nM [Ki] | |||
Target ID: CHEMBL3231 |
1.0 nM [Ki] | ||
Target ID: CHEMBL222 |
|||
Target ID: CHEMBL3231 |
|||
Target ID: CHEMBL2973 |
4.2 nM [IC50] | ||
Target ID: CHEMBL3616 |
|||
Target ID: CHEMBL2996 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Rhopressa Approved UseRHOPRESSA® (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 Date1.51346885E12 |
|||
| Primary | Rhopressa Approved UseRHOPRESSA® (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 Date1.51346885E12 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
19.5 h |
unknown, unknown |
NETARSUDIL METABOLITE AR-13503 plasma | Oryctolagus cuniculus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse 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%) Sources: Page: 6.1Eye disorders NEC (20%) Ocular signs and symptoms NEC (5 - 10) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes [Inhibition 10 uM] | ||||
| yes [Inhibition 10 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms. | 2016 Nov 1 |
|
| 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 |
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
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W6I5QDT7QI
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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OFF-TARGET->INHIBITOR |
IC50
|
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|
SALT/SOLVATE -> PARENT | |||
|
TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR |
Ki
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BINDER->LIGAND |
BINDING
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SALT/SOLVATE -> PARENT | |||
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TARGET -> INHIBITOR |
Ki
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| Related Record | Type | Details | ||
|---|---|---|---|---|
|
METABOLITE ACTIVE -> PARENT |
5 times more active than NETARSUDIL
MAJOR
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |