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A new quinazolinone compound represents a novel approach to management of choroidal neovascularization.
Philadelphia-A new quinazolinone compound (OC-10X, OcuCure Therapeutics) represents a novel approach to management of choroidal neovascularization (CNV), said Craig M. Greven, MD, here at the Macula 2011 and Atlantic Coast Retina Club meeting of the Wills Eye Institute. Administration of OC-10X was efficacious in a primate CNV model, with no evidence of ocular or systemic toxicity, he added.
Current tubulin inhibitors include the vinca alkaloids, taxols, and colchicine (used in oncology). Combretastatin is also a tubulin inhibitor used in oncology that is being investigated in age-related macular degeneration (AMD).
OC-10X is a highly lipid-soluble, low-molecular-weight quinazolinone. In a topical eye drop formulation, this compound achieves therapeutic concentrations in the vitreous, retina, and choroid, and has an excellent safety profile. It is also non-toxic, Dr. Greven said.
"Unlike other therapies for AMD, OC-10X provides the efficacy of a vascular targeting agent without the traditional toxicity associated with such drugs," he said.
OC-10X inhibits tubulin in proliferating vascular endothelial cells, and works independently of vascular endothelial growth factor and all other growth factors. OC-10X also has antiangiogenic activity, inhibiting the formation of new blood vessels.
The tubulin binding site of OC-10X is important to its mechanism of action, Dr. Greven continued. Both colchicine and combretastatin bind to the colchicine binding site of the beta subunit of tubulin. OC-10X binds in an adjacent site. Binding to an adjacent site may account for the efficacious effects and limited side-effect profile of this compound.
Data were presented at the 2008 annual meeting of the Retina Society in Scottsdale that demonstrated that topical OC-10X has significant antiangiogenic and angiolytic activity in a laser-induced model of CNV in Brown Norway rats, with reduction in CNV of 35% and 43% (p < 0.05).