vascular leakage

Diprotin A (Ile-Pro-Ile) is a dipeptidyl peptidase IV (DPP-IV) inhibitor.

Ethyl 3,4-dihydroxybenzoate (EDHB): a prolyl hydroxylase inhibitor attenuates acute hypobaric hypoxia mediated vascular leakage in brain.

TGase2-IN-1 (Compound 22) is an orally effective TGase2 inhibitor with an IC50 of 1.12 µM. It inhibits TGase2 in human retinal microvascular endothelial cells with a strikingly lower IC50 of 0.07 µM. The oral bioavailability of TGase2-IN-1 is 74.6%. Additionally, it can suppress retinal vascular leakage in a mouse model of diabetes induced by Streptozotocin.

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 protein kinase C (PKC), showing significant inhibitory activity against various PKC isoforms, including PKCα (IC50=2.4 nM), PKCβI (IC50=8.1 nM), PKCβII (IC50=6.9 nM), PKCγ (IC50=45.9 nM), and PKCθ (IC50=29.5 nM). Additionally, it can reverse retinal vascular leakage in diabetic rats.

Sozinibercept (OPT 302; VGX-300) is a soluble form of Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3) that potently inhibits the activity of Vascular Endothelial Growth Factor-C and -D (VEGF-C/D), key proangiogenic factors involved in promoting angiogenesis and vascular leakage. Additionally, Sozinibercept has been shown to inhibit diabetic retinal edema in rats [1] [2] [3].

Abicipar pegol (AGN-150998, MP0112), an anti-VEGF DARPin molecule, is a novel class of small ankyrin repeat domain-containing proteins designed for high specificity and affinity targeting. This compound effectively inhibits angiogenesis and vascular permeability, and has been applied in ocular inflammation-related disease studies through intravitreal injections, significantly reducing mean retinal thickness and leakage area [1] [2].

Faricimab, a bispecific antibody targeting Angiopoietin-2 (Ang-2) and VEGF-A. Faricimab prevents retinal ischemia/reperfusion (I/R) injury and vascular leakage, cell death, and inflammation in sCNV mouse models, showing superior visual acuity improvement over ranibizumab for retinal diseases including w-AMD, DME, and RVO.

Brolucizumab (DLX1008) is a single-chain variable fragment (scFv) anti-VEGF-A antibody exhibiting an exceptionally low picomolar binding affinity (K D = 1.05 pM). through its potent blockade of vascular endothelial growth factor A (VEGF-A), Brolucizumab effectively reduces pathological neovascularization and vascular leakage within the macula and is under investigation for the treatment of neovascular (wet) age-related macular degeneration (AMD).

CU06-1004 (Sac-1004) is an orally active compound that mitigates endothelial dysfunction by inhibiting hyperpermeability and inflammation. It reduces vascular leakage and inflammation in multiple animal models, including diabetic retinopathy, stroke, cancer, and inflammatory bowel disease. CU06-1004 also improves conditions in a CDAA-induced mouse model of NASH and enhances cardiac function [1] [2] [3].

PMX-53, a macrocyclic complement 5a (C5a) peptidomimetic and C5a receptor antagonist (IC50 = 0.3 µM), effectively inhibits the C5a-induced secretion of myeloperoxidase (MPO) in isolated human polymorphonuclear leukocytes (PMNs). Administered orally at 10 mg/kg, PMX-53 mitigates vascular leakage, PMN infiltration, and the production of TNF-α and IL-6 in a rat peritoneal Arthus reaction model. Additionally, in a 3-nitropropionic acid (3-NP)-induced Huntington's disease rat model, it alleviates body weight loss, anorexia, and striatal degeneration. Furthermore, at a dose of 3 mg/kg, PMX-53 decreases atherosclerotic lesion size and lipid content in ApoE-/- mice.

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.

Anti-ANGPT2 Antibody is a humanized monoclonal antibody expressed in CHO cells targeting Angiopoietin-2 (Ang2/ANGPT2). This product, featuring a huIgG1 heavy chain and a hukappa light chain, has a predicted molecular weight of 150 kDa. It binds specifically to Ang2 with high affinity, blocking its interaction with the Tie2 receptor. This blockade removes Ang2-mediated vascular destabilization signals, inhibiting vascular endothelial cell activation, angiogenesis, and vascular leakage.

Vasculotide, an angiopoietin-1 analog, functions as a Tie-2 activator that induces Tie-2 phosphorylation. This compound exhibits anti-inflammatory properties and enhances vascular permeability. It effectively improves endothelial barrier dysfunction induced by endotoxins and promotes angiogenesis in mouse models of diabetic ulcers. Furthermore, Vasculotide protects mice from vascular leakage and reduces mortality in mouse models of abdominal sepsis. Additionally, it decreases microvascular leakage and improves microcirculation perfusion in rat models of hemorrhagic shock.

Vasculotide TFA is an angiopoietin-1 analog and functions as a Tie-2 activator, inducing Tie-2 phosphorylation. It possesses anti-inflammatory properties and enhances barrier function in endotoxin-induced endothelial dysfunction. Additionally, Vasculotide TFA promotes angiogenesis in murine models of diabetic ulcers and protects mice from vascular leakage, reducing mortality in models of abdominal sepsis. It also reduces microvascular leakage and improves microcirculatory perfusion in rat models of hemorrhagic shock.