microvascular

INCA-6 (Triptycene-1,4-quinone) is a cell-permeable NFAT inhibitor that disrupts CN-NFAT signaling by targeting the NFAT(P) substrate at the calcineurin (CN) phosphatase site.

Tranilast (SB 252218), an antiallergic drug, suppresses lipid mediator and cytokine release from inflammatory cells, therefore utilized in the treatment of allergic disorders.

Minalrestat(ARI-509) is an orally active and potent aldose reductase inhibitor for the study of impaired microvascular reactivity in diabetic patients.

Chromocarb (Chromone-2-carboxylic acid) is a vascular protective agent used to treat venous disorders and microvascular affections.

Flavanone (2-Phenylchroman-4-one)s from citrus fruits have also been shown to exert beneficial effects on human vascular function. In particular, chronic interventions with orange juice, or the pure flavanone hesperidin, resulted in a decrease in blood pressure in overweight volunteers and acute improvements in microvascular reactivity.

Dopexamine hydrochloride (FPL60278AR) is a β2-adrenergic receptor agonist. Dopexamine can attenuate the inflammatory response and protect against organ injury in the absence of significant effects on hemodynamics or regional microvascular flow.

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.

(Z)-11,12-Epoxyeicosatrienoic acid is a potent renal microvascular dilator with anti-inflammatory properties. It inhibits leukocyte adhesion to the vascular wall by suppressing the NF-κB pathway and IκB kinase (IKK) activity. This compound is useful in studies related to vascular inflammation.

STINGantagonist-3 is a potent STING antagonist with an IC50 value of 2.3 nM against human wild-type STING. It effectively inhibits both human wild-type STING and gain-of-function STING mutants N154S and V155M. In stimulated human whole blood, STINGantagonist-3 suppresses the production of IFN-α2a. Additionally, it inhibits IP-10 production in activated human skin microvascular endothelial cells (HMVEC-d). This compound is applicable for research in autoimmune and autoinflammatory diseases, interferonopathies, and fibrotic disorders.

Albifylline is a xanthine derivates with anti-asthmatic activity. Albifylline may cause a significant reduction of shock-induced leukocyte adhesions to the sinusoidal endothelium in the liver after hemorrhagic shock. Albifylline also improves microvascula

Labradimil is a bradykinin B2 receptor agonist. Labradimil increases the permeability of human brain microvascular endothelial cell monolayers. Labradimil enhances delivery of hydrophilic chemotherapeutics and increases survival in rats with metastatic tu

(±)19(20)-EDP ethanolamide is an ω-3 endocannabinoid epoxide and cannabinoid (CB) receptor agonist (EC50s = 108 and 280 nM for CB1 and CB2, respectively). It is produced through direct epoxygenation of docosahexaenoyl ethanolamide by cytochrome P450 (CYP) epoxygenases. (±)19(20)-EDP ethanolamide (25 μM) reduces the viability of 143B metastatic osteosarcoma cells. It decreases the production of IL-6 and increases the production of IL-10 when used at concentrations ranging from 2.5 to 10 μM in BV-2 microglia stimulated by LPS and decreases LPS-induced cytotoxicity when used at concentrations ranging from 5 to 10 μM. It also decreases nitrite production when used at a concentration of 7.5 μM, an effect that can be partially reversed by the CB2 receptor antagonist AM630 and the PPARγ antagonist GW 9662 . (±)19(20)-EDP ethanolamide induces vasodilation of isolated preconstricted bovine coronary arteries (ED50 = 1.9 μM) and reduces tube formation by human microvascular endothelial cells (HMVECs) in a Matrigel assay.

Desmethylanethol trithione (ADT-OH) is a derivative of anethole dithiolethione (ADT) and synthetic hydrogen sulfide (H2S) donor. In the in vitro glucose-oxygen deprivation (OGD) model, Desmethylanethol trithione markedly attenuated tPA-enhanced Akt activation and VEGF expression in brain microvascular endothelial cells. Finally, Desmethylanethol trithione improved functional outcomes in mice subjected to MCAO and tPA infusion. H2S donors reduced tPA-induced cerebral hemorrhage by possibly inhibiting the Akt-VEGF-MMP9 cascade. Administration of H2S donors has potential as a novel modality to improve the safety of tPA following the stroke.

20-carboxy Arachidonic acid (20-COOH-AA) is the major metabolite of 20-HETE that is produced in renal tubular epithelial, endothelial, and microvascular smooth muscle cell cultures. This ω-oxidation conversion can take place using purified alcohol dehydrogenases three and four or by microsomes containing recombinant human CYP4F3B. Like 20-HETE, 20-COOH-AA inhibits ion transport in the kidneys. It also produces vasorelaxation of porcine coronary microvessels constricted with endothelin. 20-COOH-AA binds to isolated ligand binding domains of peroxisome proliferator-activated receptor α (PPARα) (Kd = 0.87 ± 0.12 μM) and PPARγ (Kd = 1.7 ± 0.5 μM), and is a dual activator of PPARα and PPARγ in a transiently transfected COS-7 cell reporter system.

1. (20R)-Protopanaxadiol ((20R)-Protopanaxdiol) has the effect of anti-tumor through increasing the activity of body immunity, inhibiting tumor interstitial microvascular density and its proliferation activity, improving the lymphocyte transformation, the activity of NK cells and the contents of IL-2 significantly. 2. (20R)-Protopanaxadiol prevents and heals obesity, fatty liver and hypertriglyceridemia in mice fed with a high-fat diet.

(R)-(4′-Hydroxy)-5,7-dihydroxy-4-chromanone, an antiangiogenic homoisoflavonoid, exhibits activity against human retinal microvascular endothelial cells (HRMECs).

1. Deoxyshikonin (Arnebin 7) may be a new drug candidate for wound healing and treatment of lymphatic diseases. 2. Deoxyshikonin enhances the ability of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) to undergo time-dependent in vitro cord formation. 3. Deoxyshikonin and dodecyl gallate show significantly synergic antimicrobial activity with penicillin in vivo and in vitro, and can effectively reduce nasopharyngeal and lung colonization caused by different penicillin-resistant pneumococcal serotypes.

JMS-053 is a potent and selective inhibitor of the phosphatase DUSP3, inhibits PTP4A3, PTP4A1, PTP4A2 and CDC25B, inhibits cancer cell migration and sphere growth, and avoids disruption of the microvascular endothelial barrier by vascular endothelial growth factor or lipopolysaccharide.

Cremastranone is a natural antiangiogenic homoisoflavanone. Cremastranone inhibits the proliferation, migration, and tube formation ability of human retinal microvascular endothelial cells.

Varisacumab (R 84) is a sophisticated human recombinant monoclonal antibody target Vascular Endothelial Growth Factor A (VEGFA), thereby effectively neutralizing its interaction with both VEGFR1 and VEGFR2 receptors. Varisacumab (R 84) has demonstrated anti-angiogenic properties in preclinical models and is extensively utilized for research involving malignancy and microvascular complications of diabetes.

L-Glutamic γ-monohydroxamate is an antitumor modified amino acid. It selectively prevents the uptake of L-histidine by microvascular endothelial cells, thereby inhibiting the proliferation of cancer cells. L-Glutamic γ-monohydroxamate is a vanadium ligand that activates vanadium-induced glucose metabolism and reduces blood glucose levels both in vitro and in vivo.

Drotrecogin alfa (activated) (DrotAA), a recombinant human activated protein C (APC), mitigates smoke-induced elevations in pulmonary microvascular permeability and proinflammatory cytokine IL-1β levels in rats. It also inhibits coagulation and inflammation while enhancing fibrinolysis. Drotrecogin alfa (activated) is applicable in severe sepsis research [1] [2].

E70K is a compound that inhibits the interaction between the chemokine (C-X-C) ligand 8 (CXCL8) and glycosaminoglycans (GAGs) on cell membrane surfaces. It mimics a segment of the CXCL8 protein's GAG-binding region at the C-terminal end, incorporating a glutamate-to-lysine mutation at the 70th position. At a concentration of 50 nM, E70K notably reduces the attachment of primary human neutrophils to human umbilical vein endothelial cells (HUVECs). Moreover, it impedes the CXCL8-triggered movement of these neutrophils across HMEC-1 human microvascular endothelial cell layers within a concentration range of 1 to 1,000 nM.

Zofenoprilat, an angiotensin-converting enzyme (ACE; IC50 = 8 nM for rabbit lung enzyme) inhibitor and the active metabolite of the prodrug zofenopril, effectively counters angiotensin I- or bradykinin-induced contractions in isolated guinea pig ileum (EC50s = 3 and 1 nM, respectively). At a concentration of 10 nM, Zofenoprilat not only diminishes basal endothelin-1 secretion and nitric oxide (NO) production but also safeguards against TNF-α-stimulated increases in reactive oxygen species (ROS) and reductions in glutathione (GSH) levels within human umbilical vein endothelial cells (HUVECs). Furthermore, at 10 µM, it delivers protection to primary human cardiac microvascular endothelial cells from doxorubicin-induced toxicity and enhances hydrogen sulfide (H2S) production, along with the adhesion, migration, and proliferation of HUVECs. Additionally, Zofenoprilat (400 µM) mitigates end diastolic pressure and lactate dehydrogenase (LDH) release, demonstrating therapeutic potential in a Langendorff isolated perfused rat heart model of ischemia-reperfusion injury.