Ocular Distribution and Pharmacodynamics of SF0166, a Topically Administered αvβ3 Integrin Antagonist, for the Treatment of Retinal Diseases

The Journal of Pharmacology and Experimental Therapeutics
Ben C AskewD Scott Edwards

Abstract

SF0166, a small-molecule αvβ3 antagonist, has physiochemical properties that allow distribution to the posterior segment of the eye after topical administration in an ophthalmic solution. The pharmacodynamics and ocular distribution of SF0166 were evaluated in several cell lines, chick chorioallantoic membrane assays, and models of ocular neovascularization in mice and pigmented rabbits. SF0166 inhibited cellular adhesion to vitronectin across human, rat, rabbit, and dog cell lines with IC50 values of 7.6 pM to 76 nM. SF0166 inhibited integrin-ligand interactions at IC50 values of 0.6-13 nM for human αvβ3, αvβ6, and αvβ8 SF0166 significantly decreased neovascularization in the oxygen-induced retinopathy mouse model. SF0166 distributed to the choroid and retina after topical ocular administration in amounts that substantially exceeded the cellular IC50 for adhesion to vitronectin; drug concentrations were maintained for >12 hours. In the laser-induced choroidal neovascularization model, topical ocular administration of SF0166 decreased lesion area compared with vehicle and was comparable to a bevacizumab injection. In the vascular endothelial growth factor-induced early neovascularization and vascular leakage model, topical ocul...Continue Reading

References

Apr 23, 2003·Experimental Cell Research·M Lourdes Ponce, Hynda K Kleinman
Dec 23, 2003·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Antonella N WitmerReinier O Schlingemann
Apr 14, 2004·Archives of Ophthalmology·Nathan CongdonUNKNOWN Eye Diseases Prevalence Research Group
Feb 3, 2005·The Journal of Clinical Endocrinology and Metabolism·M G MurphyUNKNOWN L-000845704 Study Group
Nov 24, 2005·Eye·A Foster, S Resnikoff
Aug 12, 2014·The Lancet Global Health·Rupert R A BourneUNKNOWN Vision Loss Expert Group
Jan 20, 2017·Science Translational Medicine·Raquel Lima E SilvaPeter A Campochiaro

❮ Previous
Next ❯

Citations

Jul 14, 2020·Expert Opinion on Investigational Drugs·Ashay D BhatwadekarThomas Ciulla
Sep 21, 2020·Progress in Retinal and Eye Research·Sayon Roy, Dongjoon Kim
May 19, 2021·Nature Communications·Kyle BattistonWendy Naimark
Sep 19, 2021·Nature Reviews. Drug Discovery·R J SlackR J D Hatley

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.