retinal permeability

SPHINX31 是丝氨酸 富含精氨酸的蛋白激酶1的选择性抑制剂，其IC50值为 5.9 nM。它有效抑制丝氨酸 丰富精氨酸的剪接因子1 磷酸化，有用于局部新生血管性眼病的研究潜力。

BNN27 是 TrkA 受体 (TrkA receptor) 和 p75NTR 受体 (p75NTR receptor) 的激动剂，具备神经营养和抗凋亡特性。该化合物能够提升大鼠海马和前额叶皮质中的谷氨酸、GABA 和谷氨酰胺水平，同时改善谷氨酸的代谢。在小鼠肌萎缩侧索硬化症 (ALS) 模型中，BNN27 展示了神经保护效果；在实验性自身免疫性脑脊髓炎 (EAE) 模型中显示出抗炎能力，并在大鼠糖尿病模型中具有视网膜保护功能。此外，BNN27 还能透过血脑屏障。

PB1 is a highly-effective intracellular disulfide reducing agent with notable attributes such as excellent cell permeability, the capacity to generate a substantial intracellular concentration gradient, and remarkable stability. It serves as a borane-protected TCEP (tris(2-carboxyethyl)phosphine) analogue. PB1 demonstrates the potential to enhance the survival of retinal ganglion cells following axotomy in vitro at concentrations in the nanomolar and picomolar range. Consequently, PB1 has proven instrumental in the study of neuroprotective properties[1][2][3].

PB2, a tris(2-carboxyethyl)phosphine (TCEP) analogue, enhances the survival of retinal ganglion cells (RGCs) following axotomy in vitro. Even at nanomolar and picomolar concentrations, PB2 demonstrates pronounced efficacy in promoting RGC survival. Notably, PB2 exhibits superior permeability compared to TCEP. Serving as a potent reducing agent, PB2 provides robust neuroprotection for RGCs[1].

PKC-IN-4 (compound 7l) is a highly potent and orally active inhibitor of atypical protein kinase C (aPKC), exhibiting an IC 50 value of 0.52 μM. In vitro studies have demonstrated that PKC-IN-4 effectively suppresses NF-κB activity induced by TNF-α. Moreover, this compound effectively impedes the permeability of the retinal vasculature, induced by both VEGF and TNFα. [1]

Angiogenesis inhibitor BT2 is a novel inhibitor of angiogenesis and vascular permeability, inhibiting ERK phosphorylation and the expression of FosB ΔFosB, VCAM-1, and many genes involved in proliferation, migration, angiogenesis, and inflammation, interacting with MEK1, suppressing retinal CD31, pERK, VCAM-1, and VEGF-A165 expression.

Abicipar pegol (AGN-150998, MP0112) 是一种抗VEGFDARPin 分子，DARPin 分子是一类新型的小蛋白，含有工程化的 ankyrin 重复结构域，以高特异性和亲和力与靶蛋白结合。Abicipar pegol 可有效抑制血管生成和血管通透性，通过玻璃体内注射，降低平均视网膜厚度和渗漏面积，用于眼部炎症等相关疾病研究。

Sp-8-Br-PET-cGMPS 作为一种高效的PKG激动剂，同时也担当膜渗透性视网膜型 cGMP 门控离子通道 (cGMP-gated ion channel) 的抑制剂，并激活 cGMP 依赖性蛋白激酶 I α 和 I β。该化合物在哺乳动物环核苷酸依赖性磷酸二酯酶面前表现出抗性，不产生代谢副作用。相较于 Sp-8-pCPT-cGMPS，其具有更高的亲脂性和渗透性。Sp-8-Br-PET-cGMPS 为研究神经系统中 cGMP 信号通路的作用提供了重要工具。