vascular leakage

Diprotin A (Ile-Pro-Ile) 是二肽基肽酶 IV (DPP-IV) 的抑制剂。

Ethyl 3,4-dihydroxybenzoate 是从花生种子的种皮中发现的脯氨酰羟化酶抑制剂，是一种抗氧化剂。它是胶原蛋白合成抑制剂，具有骨骼保护作用。它通过激活 NO 合酶并产生线粒体 ROS 来保护心肌，可诱导 ESCC 细胞自噬和凋亡。

TGase2-IN-1（Compound 22）为一种具口服效力的TGase2抑制剂，其对TGase2的IC50值为1.12 μM，且对人视网膜微血管内皮细胞中TGase2的抑制作用的IC50为0.07 μM。此外，TGase2-IN-1展现出74.6%的口服生物利用度，并能有效抑制小鼠Streptozotocin诱导的糖尿病模型中视网膜血管渗漏。

14,15-Leukotriene D4 (14,15-LTD4) is a member of an alternate class of LTs synthesized by a pathway involving the dual actions of 15- and 12-lipoxygenases (15- and 12-LOs) on arachidonic acid via 15-HpETE and 14,15-LTA4 intermediates. 14,15-LTD4 is classified as an eoxin (EXD4), because it is formed mostly by eosinophils. However, mast cells and nasal polyps can synthesize 14,15-LTD4 as well. Little is known about the physiological actions of 14,15-LTD4. It has weak contractile activity on both guinea pig ileum and pulmonary parenchyma in contrast to the effects of 5-LO-derived LTs. However, in an in vitro permeability assay, 14,15-LTD4 can increase vascular permeability of human endothelial cell monolayers, with similar potency to that of 5-LO-derived LTs, resulting in plasma leakage, a hallmark of inflammation.

PF-04577806 is a potent, selective, and ATP competitive inhibitor of the protein kinase C (PKC). It exhibits significant inhibitory activity against various isoforms of PKC, including PKCα, PKCβI, PKCβII, PKCγ, and PKCθ, with IC50 values of 2.4 nM, 8.1 nM, 6.9 nM, 45.9 nM, and 29.5 nM, respectively. Furthermore, PF-04577806 has the ability to reverse retinal vascular leakage in diabetic rats.

Sozinibercept (OPT 302; VGX-300) 是VEGFR-3的可溶性形式，能有效抑制血管生成原因子VEGF-C D 的活性，抑制血管生成和血管渗漏。Sozinibercept 对大鼠糖尿病视网膜水肿也有抑制作用。

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。

CU06-1004 (Sac-1004) 是一种口服活性的内皮功能障碍阻滞剂。它通过降低过度的渗透性和炎症来改善内皮功能障碍，有效抑制了包括糖尿病视网膜病变、中风、癌症和炎症性肠病在内的多种动物模型中的血管渗漏和炎症。此外，CU06-1004 对CDAA 诱导的 NASH 模型的小鼠也具有改善作用，并能够提升心脏功能。

PMX-53是一种大环型补体5a (C5a) 类肽模拟物及C5a受体的拮抗剂（IC50 = 0.3 µM）。它能抑制C5a诱导的人类分离性多形核白细胞（PMNs）中的髓过氧化物酶（MPO）分泌。在大鼠腹膜亚瑟斯反应模型中，PMX-53（10 mg kg, p.o.）能够抑制血管渗漏、多形核白细胞浸润以及腹膜TNF-α和IL-6的产生。在3-硝基丙酸（3-NP）诱导的亨廷顿病大鼠模型中，它能减少体重损失和厌食，抑制纹状体退化。PMX-53（3 mg kg）还能在ApoE- -小鼠中减小动脉粥样硬化斑块大小和脂质含量。

Leukotriene C4 (14,15-LTC4) is an inflammatory mediator synthesized from arachidonic acid through the actions of 15- and 12-lipoxygenases (LOs), involving intermediates such as 15-HpETE and 14,15-LTA4. Unlike the majority of leukotrienes formed via the 5-LO pathway, 14,15-LTC4 is an eoxin predominantly produced by eosinophils, although mast cells and nasal polyps can also synthesize it. While its physiological roles are not well understood, 14,15-LTC4 exhibits limited contractile activity on guinea pig ileum and pulmonary parenchyma. However, it can increase vascular permeability in human endothelial cell monolayers in vitro with potency comparable to 5-LO-derived leukotrienes, contributing to plasma leakage characteristic of inflammation.

Vasculotide, 一种Angiopoietin-1类似物,具有激活Tie-2并诱导其磷酸化的能力.此外,Vasculotide也表现出抗炎及抗渗透的特性.它能够改善由内毒素引起的内皮屏障功能障碍,促进小鼠糖尿病溃疡模型中的血管生成,并在小鼠模型中保护血管免受渗漏,从而降低腹腔脓毒症的死亡率.此外,Vasculotide在大鼠出血性休克模型中减少微血管渗漏,改善微循环灌注.

Vasculotide TFA，一种Angiopoietin-1类似物，作为Tie-2激活剂，能够诱导Tie-2磷酸化，展现了其抗炎和抗渗透特性。此化合物可有效改善内毒素引发的内皮屏障功能障碍，促进小鼠糖尿病溃疡模型的血管新生，保护小鼠免受血管渗漏，降低腹腔脓毒症的死亡率，并在大鼠出血性休克模型中减少微血管渗漏，改善微循环灌注。