Carboxyamidotriazole for Neovascular Ocular Disease

描述(申请人提供)：新生血管眼病，例如早产儿视网膜病变(ROP)、增殖性糖尿病视网膜病变(PDR)和“湿性”年龄相关性黄斑变性(AMD)是影响美国所有年龄段的严重疾病。近年来，以大分子血管内皮生长因子抑制剂为基础的新生血管性眼病药物治疗取得了进展。然而，需要新的药物疗法。我有新的作用机制。都是非常有效的III。可接受侵入性较小的眼部给药和静脉注射。性价比非常高。我们认为，经典的小分子合成有机药物将最好地满足这一需求，这些药物可以低成本制造，并具有高经巩膜渗透性。这项提议就是围绕这样一种小分子抗血管生成化合物--羧胺三唑(CaI)提出的。CAI具有新的作用机制，在小鼠眼部新生血管模型中显示出有效性，并具有跨巩膜通透性。在这里，我们的目的是研究计算机辅助教学的潜力，以治疗新生血管疾病通过眼部交付。为此，在第一阶段，我们将一、开发羧胺基三氮唑(CAI)眼用制剂二。在人视网膜内皮细胞和III细胞中检测其抗血管生成作用。在OIR模型和脉络膜新生血管(CNV)模型中测试最佳的眼内注射制剂(S)的玻璃体内有效性和安全性。需要新的药物治疗方法，具有新的作用机制，高效，易于接受侵入性较小的眼部给药，同时具有高成本效益。我们认为，经典的小分子合成有机药物将最好地满足这一需求，这些药物可以低成本制造，并具有高经巩膜渗透性。

DESCRIPTION (provided by applicant): Neovascular ocular diseases as exemplified by retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR) and "wet" age-related macular degeneration (AMD) are severe diseases affecting all age groups in the US. Recently, there has been progress in neovascular ocular disease drug therapy based on large molecule VEGF inhibitors. Nevertheless, novel drug therapies are needed that i. have new mechanisms of action ii. are highly efficacious iii. are amenable to less invasive ocular administration and iv. are highly cost effective. We believe that this need will best be met with classical small molecule synthetic organic drugs that can be manufactured at low cost and have high transcleral permeability. This proposal centers on just such a small molecule anti- angiogenic compound, carboxyamidotriazole (CAI). CAI has a novel mechanism of action, demonstrated efficacy in mouse ocular neovascularization models and has transcleral permeability. Herein, we aim study the potential of CAI to treat neovascular disease by ocular delivery. To this end in Phase I we will i. develop ocular formulations of carboxyamidotriazole (CAI) ii. test the anti-angiogenic effects of CAI in human retinal endothelial cells and iii. test the intravitreal ocular efficacy and safety of optimal CAI formulation(s) in the OIR model and choroidal neovascularization (CNV) models. Novel drug therapies are needed that have new mechanisms of action are highly efficacious and amenable to less invasive ocular administration while being highly cost effective. We believe that this need will best be met with classical small molecule synthetic organic drugs that can be manufactured at low cost and have high transcleral permeability.