> Publications > Identification of Nitric Oxide-Donating Ripasudil Derivatives with Intraocular Pressure Lowering and Retinal Ganglion Cell Protection Activities

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Publication

June 7, 2023 • ✎ STRIA TECH

Identification of Nitric Oxide-Donating Ripasudil Derivatives with Intraocular Pressure Lowering and Retinal Ganglion Cell Protection Activities

Topics:

Glaucoma

The Optic Nerve, its Neurons and Diseases

Publication

Journal of Medicinal Chemistry (Sep 08, 2022) Identification of Nitric Oxide-Donating Ripasudil Derivatives with Intraocular Pressure Lowering and Retinal Ganglion Cell Protection Activities

Yang Z, Wu J, Wu K, Luo J, Li C, Zhang J, Zhao M, Mei T, Liu X, Shang B, Zhang Y, Zhao L, Huang Z

DOI: 10.1021/acs.jmedchem.2c00600 >>

Ripasudil (trade name Glanatec) is a rho kinase inhibitor drug used for the treatment of glaucoma and ocular hypertension. Yang et al tested 6 new derivatives of ripasudil in chronic ocular hypertension glaucoma mice, and found that one of them, RNO-6, showed superior efficacy compared to ripasudil.

Based on the synergistic therapeutic effect of nitric oxide (NO) and Rho-associated protein kinase (ROCK) inhibitors on glaucoma, a new group of NO-donating ripasudil derivatives RNO-1-RNO-6 was designed, synthesized, and biologically evaluated. The results demonstrated that the most active compound RNO-6 maintained potent ROCK inhibitory and NO releasing abilities, reversibly depolymerized F-actin, and suppressed mitochondrial respiration in human trabecular meshwork (HTM) cells. Topical administration of RNO-6 (0.26%) in chronic ocular hypertension glaucoma mice exhibited significant IOP lowering and visual function and retinal ganglion cell (RGC) protection activities, superior to an equal molar dose of ripasudil. RNO-6 could be a promising agent for glaucoma or ocular hypertension, warranting further investigation.