netarsudil   

GtoPdb Ligand ID: 9322

Synonyms: AR-11324 | AR11324 | ester 60 [PMID: 27072905] | Rhokiinsa® | Rhopressa®
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.
2D Structure
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Physico-chemical Properties
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
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
No information available.
Summary of Clinical Use
An ophthalmic solution containing netarsudil was approved by the FDA in December 2017 for the treatment of glaucoma or ocular hypertension, following successful Phase 3 clinical trial [4]. Click here to link to the Phase 3 netarsudil (research code AR-13324) trials registered with ClinicalTrials.gov.
Mechanism Of Action and Pharmacodynamic Effects
Inhibition of Rho kinase improves fluid outflow through the trabecular meshwork to lower intraocular pressure. The full action of netarsudil involves multiple mechanisms, including changes to outflow hydrodynamics and ocular morphology [3].