netarsudil   Click here for help

GtoPdb Ligand ID: 9322

Synonyms: AR-11324 | AR11324 | ester 60 [PMID: 27072905] | Rhokiinsa® | Rhopressa®
Approved drug
netarsudil is an approved drug (FDA (2017), EMA (2019))
Compound class: Synthetic organic
Comment: Netarsudil (AR-11324) is a combination Rho-associated protein kinase (Rho or ROCK) and norepinephrine transporter (NET) inhibitor [2,5]. Netarsudil is the S-enantiomeric, 2,4-dimethyl benzoate ester of compound 29 (Ki 0.2nM) described in [5]. Esterification improves bioavailability and corneal penetrating ability of the compound. It is an ocular hypotensive medication.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 94.31
Molecular weight 453.21
XLogP 4.35
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES NCC(C(=O)Nc1ccc2c(c1)ccnc2)c1ccc(cc1)COC(=O)c1ccc(cc1C)C
Isomeric SMILES NC[C@@H](C(=O)Nc1ccc2c(c1)ccnc2)c1ccc(cc1)COC(=O)c1ccc(cc1C)C
InChI 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
InChI Key OURRXQUGYQRVML-AREMUKBSSA-N
References
1. Dayal N, Mikek CG, Hernandez D, Naclerio GA, Yin Chu EF, Carter-Cooper BA, Lapidus RG, Sintim HO. (2019)
Potently inhibiting cancer cell migration with novel 3H-pyrazolo[4,3-f]quinoline boronic acid ROCK inhibitors.
Eur J Med Chem, 180: 449-456. DOI: 10.1016/j.ejmech.2019.06.089 [PMID:31330446]
2. Lin CW, Sherman B, Moore LA, Laethem CL, Lu DW, Pattabiraman PP, Rao PV, deLong MA, Kopczynski CC. (2018)
Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma.
J Ocul Pharmacol Ther, 34 (1-2): 40-51. [PMID:28609185]
3. Ren R, Li G, Le TD, Kopczynski C, Stamer WD, Gong H. (2016)
Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms.
Invest Ophthalmol Vis Sci, 57 (14): 6197-6209. [PMID:27842161]
4. Serle JB, Katz LJ, McLaurin E, Heah T, Ramirez-Davis N, Usner DW, Novack GD, Kopczynski CC, ROCKET-1 and ROCKET-2 Study Groups. (2018)
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).
Am J Ophthalmol, 186: 116-127. [PMID:29199013]
5. Sturdivant JM, Royalty SM, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong MA. (2016)
Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma.
Bioorg Med Chem Lett, 26 (10): 2475-80. [PMID:27072905]