NCX 470 is a Nitric Oxide (NO)-Donating Prostaglandin Analogue

Glaucoma is a type of eye disease that may cause optic nerve damage and vision loss. The predominant risk factor for the progression of glaucoma is an elevated intraocular pressure (IOP) due to reduced aqueous humor (AH) outflow facility through the trabecular meshwork and Schlemm\’s canal outflow pathway (i.e., conventional pathway).

Prostaglandins elicit various biological effects including regulation of smooth muscles, inflammation, and immune response. Prostaglandin F2α (PGF2α) analogues have ocular hypotensive effects, mainly acting by increasing uveoscleral outflow. Moreover, the complementary mode of action of PGs and NO in the eye is best evidenced in recently identified compounds combining FP agonistic activity and NO‐mediated GC activation/cGMP formation. Therefore, such compounds have the potential for the research of ocular hypertension and glaucoma.

NCX 470 is a second-generation nitric oxide (NO)-donating Prostaglandin analogue.

\"\"

From: Jeong H, et al. Mol Pharm. 2020 Feb 3;17(2):656-665.

This compound is a NO-donating Bimatoprost carrying an NO moiety esterified with the hydroxyl group present in the position of the Bimatoprost structure. NCX 470 acts primarily through the relaxation of trabecular meshwork and Schlemm\’s canal. Thus, it has the potential to research the reduction of intraocular pressure (IOP) with open-angle glaucoma or ocular hypertension. This compound lowers IOP more than equimolar Bimatoprost in animal models of glaucoma by activating PGF2α and NO/cGMP signaling pathways. Particularly, NCX 470 is effective in lowering IOP in transient hypertonic saline-induced IOP elevation (tOHT-rabbits) as well as in normotensive dogs (ONT-dogs) and nonhuman primates with unilateral laser-induced ocular hypertension (OHT-monkeys). Furthermore, this compound has good safety and efficacy in all tested species.

To sum up, NCX 470 is a NO-donating Prostaglandin analogue and has the potential to research glaucoma or ocular hypertension.

References:

[1] Francesco Impagnatiello, et al. Invest Ophthalmol Vis Sci. 2015 Oct;56(11):6558-64.

[2] Francesco Impagnatiello, et al. Br J Pharmacol. 2019 Apr;176(8):1079-1089.