Netarsudil is a synthetic Rho-associated protein kinase (ROCK) inhibitor and norepinephrine transporter inhibitor used as a pharmaceutical active pharmaceutical ingredient (API). It acts primarily on pathways involved in aqueous humor dynamics and is associated with the management of elevated intraocular pressure (IOP) in ophthalmic applications.
Netarsudil is an important ophthalmic pharmaceutical compound used in the development and manufacture of formulations for glaucoma and ocular hypertension.
Netarsudil is a specialized ophthalmic API relevant to glaucoma drug development, ocular pharmacology, pharmaceutical formulation research and analytical quality control.
The compound is commonly encountered in pharmaceutical development as Netarsudil Mesylate, the salt form used in ophthalmic drug products. FDA documentation identifies Netarsudil Mesylate as the drug substance for the approved ophthalmic product.
CAS Number: 1254032-66-0
Molecular Formula: C₂₈H₂₇N₃O₃
Molecular Weight: 453.5 g/mol
IUPAC Name: [4-[(2S)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 2,4-dimethylbenzoate
Development Code: AR-13324 / AR-13324 free base
Drug Class: Rho Kinase Inhibitor
Therapeutic Class: Ophthalmic Antiglaucoma Agent
Therapeutic Area: Ophthalmology
Molecule Type: Synthetic Small Molecule
Primary Targets: ROCK and Norepinephrine Transporter (NET)
PubChem reports the molecular formula as C₂₈H₂₇N₃O₃ and molecular weight as 453.5 g/mol.
Netarsudil acts as a ROCK inhibitor and also inhibits the norepinephrine transporter.
Its pharmacological effects include:
These mechanisms contribute to the IOP-lowering activity of netarsudil.
Netarsudil API is relevant to:
Netarsudil ophthalmic preparations are associated with reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.
Its dual pharmacological activity involving ROCK inhibition and norepinephrine transporter inhibition provides a mechanism for increasing aqueous humor outflow and reducing factors contributing to elevated IOP.
Rho-associated protein kinase is involved in cellular contractility and regulation of the trabecular meshwork.
Netarsudil inhibits ROCK signaling, promoting relaxation of the trabecular meshwork and facilitating trabecular aqueous humor outflow. This mechanism distinguishes netarsudil from many conventional glaucoma medications.
Netarsudil free base has a molecular formula of C₂₈H₂₇N₃O₃ and molecular weight of 453.5 g/mol. PubChem reports an XLogP3-AA value of approximately 4.6 and topological polar surface area of approximately 94.3 Ų.
For pharmaceutical manufacturing, Netarsudil is commonly handled as Netarsudil Mesylate. FDA documentation describes Netarsudil Mesylate drug substance as a light yellow to white powder.
A controlled Netarsudil API manufacturing process may involve:
Typical Netarsudil Mesylate API testing may include:
FDA quality documentation confirms that Netarsudil Mesylate drug substance specifications include identification by FTIR and HPLC, assay, chromatographic purity, total impurities, residual-solvent testing and water-content testing.
Store Netarsudil API in a tightly closed container under controlled pharmaceutical storage conditions, protected from excessive moisture, heat and direct light.
Commercial storage conditions should be based on validated stability data and the applicable API specification.
| Parameter | Specification |
|---|---|
| Appearance | White crystalline powder or crystals |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |