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1 General aspects (0)   1.1 Epidemiology (5)   1.2 Population genetics (0)   1.3 Pathogenesis (3)   1.4 Quality of life (8)   1.5 Glaucomas as cause of blindness (4)   1.6 Prevention and screening (11) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (7)   2.2 Cornea (21)   2.3 Sclera (13)   2.4 Anterior chamber angle (7)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (4)     2.5.2 Schlemms canal (1)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (0)     2.6.1 Production (0)     2.6.2 Outflow (2)       2.6.2.1 Trabecular meshwork (4)       2.6.2.2 Uveoscleral (1)     2.6.3 Compostion (5)   2.7 Episcleral veins and venous pressure (0)   2.8 Iris (4)   2.9 Ciliary body (3)   2.10 Lens (0)   2.11 Vitreous body (0)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (12)   2.13 Retina and retinal nerve fibre layer (35)   2.14 Optic disc (26)   2.15 Optic nerve (6)   2.16 Chiasma and retrochiasmal central nervous system (16)   2.17 Stem cells (4)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (1)   3.2 Electron microscopy (0)   3.3 Immunohistochemistry (1)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (0)     3.4.2 Gene studies (33)   3.5 Molecular biology incl. SiRNA (16)   3.6 Cellular biology (30)   3.7 Biochemistry (9)   3.8 Pharmacology (14)   3.9 Pathophysiology (3)   3.10 Immunobiology (6)   3.11 Pharmacogenetics (0)   3.12 Proteomics (0)   3.13 In vivo imaging (0)     3.13.1 Laser Scanning (0)       3.13.1.1 Confocal Scanning Laser Ophthalmoscopy (0)       3.13.1.2 Confocal Scanning Laser Polarimetry (0)     3.13.2 Optical Coherence Tomography (0)       3.13.2.1 Anterior Segment (0)       3.13.2.2 Posterior Segment (1)     3.13.3 RGC Imaging (3)     3.13.4 Other (1)   3.20 Other (1) 4 Tissue culture of ocular cells (0) 5 Experimental glaucoma; animal models (0)   5.1 Rodent (35)   5.2 Primates (1)   5.3 Other (11) 6 Clinical examination methods (0)   6.1 Intraocular pressure measurement; factors affecting IOP (0)     6.1.1 Devices, techniques (17)     6.1.2 Fluctuation, circadian rhythms (5)     6.1.3 Factors affecting IOP (21)   6.2 Tonography, aqueous flow measurement (see also 2.6) (2)   6.3 Biomicroscopy (slitlamp) (0)     6.3.1 Anterior segment (1)     6.3.2 Posterior segment (0)   6.4 Gonioscopy (0)   6.5 Ophthalmoscopy (0)   6.6 Visual field examination and other visual function tests (0)     6.6.1 Conventional manual (1)     6.6.2 Automated (17)     6.6.3 Special methods (e.g. color, contrast, SWAP etc.) (7)   6.7 Electro-ophthalmodiagnosis (7)   6.8 Photography (0)     6.8.1 Anterior segment (1)     6.8.2 Posterior segment (9)   6.9 Computerized image analysis (0)     6.9.1 Laser scanning (0)       6.9.1.1 Confocal Scanning Laser Ophthalmoscopy (7)       6.9.1.2 Confocal Scanning Laser Polarimetry (1)     6.9.2 Optical coherence tomography (0)       6.9.2.1 Anterior (13)       6.9.2.2 Posterior (47)     6.9.5 Other (3)   6.10 Fluorescein (ICG) angiography (0)     6.10.1 Anterior segment (0)     6.10.2 Posterior segment (0)   6.11 Bloodflow measurements (21)   6.12 Ultrasonography and ultrasound biomicroscopy (4)   6.13 Provocative tests (1)   6.19 Telemedicine (2)   6.20 Progression (13)   6.30 Other (6) 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    12.8.1 Without tube implant (28)     12.8.2 With tube implant or other drainage devices (32)     12.8.3 Non-perforating (7)     12.8.4 Using laser (0)     12.8.5 Other (2)     12.8.10 Woundhealing antifibrosis (16)     12.8.11 Complications, endophthalmitis (10)   12.9 Trabeculotomy, goniotomy (17)   12.10 Cyclodestruction (4)   12.11 Cyclodialysis (0)   12.12 Cataract extraction (0)     12.12.1 Intracapsular (0)     12.12.2 Extracapsular (1)     12.12.3 Phacoemulsification (11)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (0)     12.14.3 Phacoemulsification (8)   12.15 Capsulotomy (0)   12.16 Vitrectomy (0)   12.17 Anesthesia (0)   12.20 Other (4) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (2)   13.2 Outcome (0)     13.2.1 IOP (4)     13.2.2 Visual field (0)       13.2.2.1 Progression (0)       13.2.2.2 Improvement (1)     13.2.3 Other (0) 14 Costing studies; pharmacoeconomics (2) 15 Miscellaneous (25)

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Abstract #67164 Published in IGR 17-4

Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma

Sturdivant JM; Royalty SM; Lin CW; Moore LA; Yingling JD; Laethem CL; Sherman B; Heintzelman GR; Kopczynski CC; deLong MA
Bioorganic and Medicinal Chemistry Letters 2016; 26: 2475-2480

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Inhibition of Rho kinase (ROCK) to improve fluid outflow through the trabecular meshwork and lower intraocular pressure is a strategy for the development of new anti-glaucoma agents. Alpha-aryl-beta-amino isoquinoline analogs were identified as potent ROCK inhibitors. Compounds that provided a longer duration of intraocular pressure reduction in Dutch Belted rabbits also inhibited norepinephrine transporter. Ester 60 improved bioavailability of its parent ROCK inhibitor, 29 (Ki=0.2nM) and demonstrated an effective and sustained IOP reduction for 24h after dosing. From these studies, netarsudil (a.k.a. AR-13324) was discovered and is currently in clinical trials for the treatment of glaucoma and ocular hypertension.

Aerie Pharmaceuticals, Inc., 4301 Emperor Boulevard, Suite 400, Durham, NC 27703, United States. Electronic address: jsturdivant@aeriepharma.com.

Full article

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Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)

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