2018
DOI: 10.1124/jpet.118.248427
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Ocular Distribution and Pharmacodynamics of SF0166, a Topically Administered αvβ3 Integrin Antagonist, for the Treatment of Retinal Diseases

Abstract: SF0166, a small-molecule 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 IC values of 7.6 pM to 76 nM… Show more

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Cited by 22 publications
(12 citation statements)
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“…Ophthalmic exams, including fundus microscopy and slit lamp microscopy, were carried out over the 3 days post-VEGF induction and vascular leakage was measured by fluorescein angiography on the third day post-VEGF induction. Eyes were graded based on fundus and fluorescein angiography images using a scoring system as follows 76 : 0 – major vessels straight, some tortuosity of smaller vessels, no vessel dilation; 1 – increased tortuosity of major vessels and/or some vessel dilation; 2 – leakage between major vessels, significant vessel dilation; 3 – leakage between major and minor vessels, minor vessels still visible; and 4 – leakage between major and minor vessels, minor vessels poorly/not visible.…”
Section: Methodsmentioning
confidence: 99%
“…Ophthalmic exams, including fundus microscopy and slit lamp microscopy, were carried out over the 3 days post-VEGF induction and vascular leakage was measured by fluorescein angiography on the third day post-VEGF induction. Eyes were graded based on fundus and fluorescein angiography images using a scoring system as follows 76 : 0 – major vessels straight, some tortuosity of smaller vessels, no vessel dilation; 1 – increased tortuosity of major vessels and/or some vessel dilation; 2 – leakage between major vessels, significant vessel dilation; 3 – leakage between major and minor vessels, minor vessels still visible; and 4 – leakage between major and minor vessels, minor vessels poorly/not visible.…”
Section: Methodsmentioning
confidence: 99%
“…One of those drugs is the integrin αVβ3 antagonist SF-0166 (OcuTerra Therapeutics, Boston, MA, USA; for-merly SciFluor Life Sciences, Inc., Boston, MA, USA). Preclinical investigations in rabbits showed a good pharmacokinetic profile, and the efficacy results of topical administration in laser-induced and VEGF-induced CNV rabbit models were comparable to a bevacizumab injection [103]. Furthermore, biological effects and good tolerability have been shown in early clinical trials with diabetic macular edema [112] and neovascular AMD patients, which underlines the potential of targeting RGD-binding integrins, to develop a nextgeneration therapy for retinal diseases [111].…”
Section: Innovative Small Moleculesmentioning
confidence: 96%
“…Further regarding the preclinical pharmacokinetic studies performed on rabbits, it is surprising to note that a common procedure when investigating topical retinal treatments is the pooling together of choroid and retina tissues and then measuring the average drug concentration in both tissues (Shikamura et al, 2016;Askew et al, 2018;Horita et al, 2019;Huang et al, 2021). However, this makes it difficult to conclude the real drug exposure exclusively in the neural retina.…”
Section: Further Insidementioning
confidence: 99%
“…The rabbit study collection is non-exhaustive but intends to be representative of the variety of drugs investigated in albino and pigmented eyes (Urtti et al, 1990;Acheampong et al, 2002;Sigurdsson et al, 2005;Chastain et al, 2016;Askew et al, 2018;Johannsdottir et al, 2018;Fayyaz et al, 2021), while the patient data are comprehensive and obtained from patients who underwent enucleation or vitrectomy surgery for therapeutic reasons (Kent et al, 2001;Holló et al, 2006;Heier et al, 2009). Only patients with a healthy status of the lens (phakic) were selected since it is known that the lack of a lens affects ocular pharmacokinetics (Maurice et al, 1984;Mandell et al, 1993).…”
Section: Further Insidementioning
confidence: 99%
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