Bioengineering, University of Pittsburgh, USA.
Sorbonne Université, INSERM, Institut de la Vision, Paris, France.
Exp Eye Res. 2021 Dec;213:108861. doi: 10.1016/j.exer.2021.108861. Epub 2021 Nov 22.
Aberrant angiogenesis lies at the heart of a wide range of ocular pathologies such as proliferative diabetic retinopathy, wet age-related macular degeneration and retinopathy of prematurity. This study explores the anti-angiogenic activity of a novel small molecule investigative compound capable of inhibiting profilin1-actin interaction recently identified by our group. We demonstrate that our compound is capable of inhibiting migration, proliferation and angiogenic activity of microvascular endothelial cells in vitro as well as choroidal neovascularization (CNV) ex vivo. In mouse model of laser-injury induced CNV, intravitreal administration of this compound diminishes sub-retinal neovascularization. Finally, our preliminary structure-activity relationship study (SAR) demonstrates that this small molecule compound is amenable to improvement in biological activity through structural modifications.
异常血管生成是多种眼部病变的核心，如增生性糖尿病视网膜病变、湿性年龄相关性黄斑变性和早产儿视网膜病变。本研究探索了一种新型小分子研究化合物的抗血管生成活性，该化合物能够抑制我们小组最近发现的原肌球蛋白 1-肌动蛋白相互作用。我们证明，我们的化合物能够抑制体外微血管内皮细胞的迁移、增殖和血管生成活性，以及脉络膜新生血管（CNV）的体外生成。在激光诱导的 CNV 小鼠模型中，玻璃体内给予该化合物可减少视网膜下新生血管。最后，我们的初步结构-活性关系研究（SAR）表明，通过结构修饰，这种小分子化合物可以提高其生物活性。
