acute lung injury

Dexmedetomidine hydrochloride (Precedex) is a potent, selective, orally active α2-adrenoceptor agonist with a Ki value of 1.08 nM. It shows 1620-fold selectivity over α1-adrenoceptors. Dexmedetomidine hydrochloride (Precedex) can protect against sepsis-induced acute lung injury through anti-inflammatory, anti-oxidative, and anti-apoptotic effects.

Matrine (Vegard), an alkaloid isolated from the Sophora genus, acts as a kappa opioid receptor agonist.

Sivelestat (ONO5046) is a potent and selective inhibitor of neutrophil elastase with IC50 of 44 nM.

Pemetrexed disodium (LY-231514) is a parenterally administered folate antagonist and antineoplastic agent, used in the treatment of non-small cell lung cancer and malignant mesothelioma. Pemetrexed disodium therapy has been associated with moderate rates of serum enzyme elevations during therapy, but has not been convincingly linked to instances of acute, clinically apparent liver injury.

Nrf2 activator-1 is a potent activator of NF-E2-related factor 2 (Nrf2) and can be used to study COPD and other respiratory diseases, including asthma, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and pulmonary fibrosis.

GW274150 is an orally active, selective and potent dual inhibitor of NADPH-dependent human nitric oxide synthase (iNOS) (Kd=40 nM) and rat inducible nitric oxide synthase (iNOS).GW274150 has a low activity against endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) in humans and rats. GW274150 showed protective effects in an inflammatory model of acute lung injury.

N-Oleoyl valine is an endogenous N-acyl amine that acts as an antagonist at the transient receptor potential vanilloid type 3 (TRPV3) receptor, which is involved in thermoregulation. N-Oleoyl valine is increased in mice following cold exposure for up to at least 16 days. Acute lung injury in mice increases the concentration of N-Oleoyl valine in lung tissue. N-acyl amines also promote mitochondrial uncoupling.

Phillyrin (Forsythin) is a novel AMPK activator, has anti-obesity effects in nutritive obesity mice, it can prevent lipid accumulation in HepG2 cells by blocking the expression of SREBP-1c and FAS through LKB1 AMPK activation. Phillyrin(Forsythin) may be a new preventive agent of acute lung injury in the clinical setting, it potentially contributes to the suppression of the activation of MAPK and NF-κB pathways, it also has protective effects on H2O2-induced oxidative stress and apoptosis in PC12 cells.

Piceatannol (Astringenin) is an anti-inflammatory, immunomodulatory and antiproliferative agent. It inhibits p56lck and syk protein tyrosine kinases and inhibits NF-κB activation and gene expression of TNF-induced. It is synthetic from the conversion of resveratrol by cytochrome P450 1B1.

1. Peimisine (Ebeiensine) can affect M-receptor, excit β-receptor, restrain the release of internal calcium, and promote to releaseing nitrogen monoxidum in order to relax tracheal smooth muscle and relieve asthma. 2. Peimisine can attenuate lung tissue injury( ALI), LDH and MDA amount in ALI mice in a dose dependent manner, it also lower the total protein, total white blood cells, lymphocyte and neutrophilic leukocyte in bronchoalveolar lavage fluid( BALF); suggests that peimisine can play a protective role against LPS-induced acute lung injury. 3. Peimisine has the protective effect on the experimental hepatic fibrosis formation, the possible mechanisms are associated with inhibiting fibrogenesis and fibrosis accumulation, and decreasing lipid peroxidation. 4. Peimisine can inhibit angiotensin I converting enzyme activity in a dose-dependent manner, displaying 5 % inhibitory concentration values of 526.5 microM, thus, it may have antihypertensive action.

Manganese(salen) chloride (EUK-8) is a superoxide dismutase and catalase mimetic, serving as an antioxidant with oxyradical scavenging properties, and ameliorates acute lung injury in endotoxemic swine.

HCH6-1 is a competitive Formyl peptide receptor 1 (FPR1) antagonist.

Sivelestat sodium tetrahydrate (ONO5046 sodium tetrahydrate) is a competitive inhibitor of human neutrophil elastase, with an IC50 of 44 nM and a Ki of 200 nM. Sivelestat (EI546) sodium tetrahydrate has the potential for the study of acute lung injury acute respiratory distress syndrome or disseminated intravascular coagulation in COVID-19.

Ac2-26 acetate is an active N-terminal peptide of annexin A1(AnxA1). Ac2-26 acetate decreases AnxA1 protein expression and inhibits the activation of NF-κB and MAPK pathways in the injured lung tissue. Ac2-26 acetate attenuates ischemia-reperfusion-induced acute lung injury.

1-Hydroxy-2,3,5-trimethoxyxanthone (HM-1) exhibits vasodilator action through an endothelium-dependent mechanism involving NO and an endothelium-independent mechanism by inhibiting Ca(2+) influx via L-type voltage-operated Ca(2+) channels. A minor contribution to HM-1's effects may stem from inhibiting protein kinase C-mediated release of intracellular Ca(2+) stores. At 1 µg mL, HM-1 effectively inhibits osteoclast differentiation in co-cultures with mouse osteoblastic calvarial and bone marrow cells and protects mice from acute lung injury induced by lipopolysaccharide (LPS), likely by increasing IκB-α protein expression and suppressing inducible nitric oxide synthase and cyclooxygenase-Ⅱ protein expression.

Nezulcitinib (TD-0903) is an inhaled, lung-selective pan-Janus kinase (JAK) inhibitor used to study COVID-19-associated acute lung injury and impaired oxygenation.

AZD1236 is a potent and reversible inhibitor of human MMP-9 and MMP-12 (IC50 = 4.5 and 6.1nM, respectively), with >10-fold selectivity to MMP-2 and MMP-13 and >350-fold selectivity to other members of the enzyme family. AZD1236 activity is approximately 20 to 50-fold lower at the rat, mouse, and guinea pig orthologues. In acute models of lung injury, AZD1236 inhibited the haemorrhage and inflammation induced by instillation of human MMP-12 into rat lungs by ~80% at 0.81mg/kg, and also abolished macrophage infiltration into BAL fluid induced by tobacco smoke inhalation in the mouse.

(±)9(10)-DiHOME, the diol derivative of (±)9(10)-EpOME—a cytochrome P450-derived epoxide of linoleic acid also known as leukotoxin—is formed through the action of soluble epoxide hydrolase (sEH) in neutrophils. It exhibits toxicity towards Sf21 cells expressing sEH as well as tolacZ-expressing control cells, differing from leukotoxin which only harms sEH-containing cells. Furthermore, combined exposure to 9(10)- and 12(13)-DiHOME leads to cell death in rabbit renal proximal tubule cells by disrupting mitochondrial respiration, and causes lung injury, respiratory distress, and mortality in mice, highlighting its role as a toxic lipid mediator. Specifically, 9(10)-DiHOME has been associated with acute respiratory distress syndrome (ARDS), a severe and often deadly complication in patients with major burns. Elevated levels of this compound have been detected in the bronchoalveolar lavage fluid (BALF) of women, but not men, with chronic obstructive pulmonary disease (COPD), and its levels are also increased in patients with allergic asthma, indicating its significance in respiratory conditions.

BRL 44408 Maleate is a potent α2A-adrenoceptor antagonist with antidepressant and analgesic activity that reduces lipopolysaccharide (LPS)-induced expression and attenuates endogenous lipopolysaccharide-induced acute lung injury through inhibition of the mitogen-activated protein kinase kinase extracellularly regulated protein kinase signaling pathway in mice.

Daxdilimab, an anti-ILT7 monoclonal antibody, targets the ILT7 cell surface molecule exclusive to pDC dendritic cells. It shows potential for treating acute lung injury (ALI) in COVID-19 infected patients, as indicated in research [1] [2].

FTY720 (S)-Phosphate, an S1P receptor 1 (S1PR1) agonist, is utilized in research on acute inflammatory diseases, including acute lung injury.

ACT-660602 is an orally active chemokine receptor CXCR3 antagonist (IC50: 204 nM) that inhibits T cell migration and has demonstrated significant efficacy in an in vivo model of acute lung injury. It is useful for studying autoimmune diseases.

TREM-1 inhibitory peptide M3 acts as a ligand-dependent antagonist of TREM-1, capable of suppressing systemic and pulmonary pro-inflammatory cytokine and chemokine production, thereby mitigating acute lung injury [1].

Antileukinate is a synthetic hexapeptide with an acetylated amino terminus and an amidated carboxyl terminus that inhibits the binding of CXC chemokines to the chemokine receptor CXCR2. It inhibits IL-8 binding to neutrophils (Ki = 2.7-13 μM), prevents neutrophil chemotaxis and β-glucuronidase release, and blocks IL-8-induced skin edema in rabbits. At 53 mg/kg, antileukinate has been shown to protect mice against acute pancreatitis and associated lung injury.

PI3Kδ-IN-14 (Compound (S)-29), a selective PI3Kδ inhibitor with an IC50 of 0.8 nM and a Kd of 84.8 nM, targets the ATP-binding site within the kinase domain of PI3Kδ, exhibiting anti-inflammatory properties by impeding the PI3K AKT pathway and alleviating acute lung injury (ALI) [1].

Anti-inflammatory agent 50 (compound a1), a derivative of Fusidic acid, exerts its effects through inhibition of inflammatory mediators including NO, IL-6, and TNF-α. It mitigates acute lung injury by modulating these mediators and suppressing the MAPK, NF-κB, and NLRP3 inflammasome signaling pathways [1].

Antidesmone is one compound mainly isolated from Ajugade cumbers Thunb (Labiatae). Antidesmone prevents acute lung injury via regulating MAPK and NF-κB activities.

PNU-282987 (free base) is a potent agonist of α7 nicotinic acetylcholine receptor (nAChR) with an EC50 of 154 nM and a functional antagonist of the 5-HT3 receptor with an IC50 of 4541 nM. It can be used for central and peripheral nervous system studies[1].

NF-κB-IN-8 is a competitive antagonist of LPS for MD-2 binding, and it impedes the expression of inflammatory factors by engaging MD-2. Additionally, it inhibits ALP activity and is usable in inflammation research, including acute lung injury (ALI) [1].

Tylvalosin (Acetylisovaleryltylosin) is a broad-spectrum macrolide antibiotic with antibacterial and antiviral properties, effective against PRRSV infection. It induces apoptosis and possesses anti-inflammatory activity. Furthermore, Tylvalosin mitigates oxidative stress and acute lung injury through the suppression of NF-κB activation [1] [2].

iNOs-IN-3 is an orally active nitric oxide synthase (iNOS) inhibitor with an IC50 value of 3.342 μM that exhibits anti-inflammatory effects and can be used to study LPS-induced acute lung injury (ALI).

1. Ruscogenin has anti-inflammatory activity, suppressed zymosan A-evoked peritoneal total leukocyte migration in mice in a dose-dependent manner, 2. Ruscogenin inhibited adhesion of leukocytes to a human umbilical vein endothelial cell line (ECV34) injured by tumor necrosis factor-alpha (TNF-alpha) in a concentration-dependent manner. 3. Ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-kappa B p65 activation.

JNK2-IN-1 (Compound J27), a selective JNK2 inhibitor with a dissociation constant (Kd) of 79.2 µM, exhibits anti-inflammatory effects by attenuating TNF-α and IL-6 secretion via inhibition of the NF-κB/MAPK pathway. It effectively mitigates symptoms associated with LPS-induced acute lung injury (ALI) and sepsis [1].

Anti-inflammatory agent 51 is an amide sulfonamide derivative with anti-inflammatory and potentially anti-tumor activity and inhibition of NF-κB activation, which can be used to study acute lung injury and ulcerative colitis.

Manassantin B is a potent inhibitor of NF-κB activation by the suppression of transciptional activity of RelA/p65 subunit of NF-κB. It also possesses anti-EBV lytic replication activity. Manassantin B inhibits interleukin-6-induced signal transducer and activator of transcription 3 activation in Hep3B cells, it has potential as a potent anti-inflammatory drug for use in pathological processes such as sepsis or acute lung injury. Manassantin B exerts antifibrotic activity in HSC-T6 cells, in part, via inhibition of cell proliferation and decrease of collagen production.

1. Sauchinone is a useful adjunctive treatment for bacterial infection. 2. Sauchinone, an active lignan found in Saururus chinensis, to regulate the activation of HSCs, to prevent liver fibrosis, and to inhibit oxidative stress in vivo and in vitro. 3. Sa

TRPV4 antagonist 4, a potent inhibitor of TRPV4 with an IC50 of 22.65 nM, effectively blocks TRPV4 current and demonstrates protective properties against acute lung injury [1].

Taxamairin B is a potent anti-inflammatory compound that inhibits the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and reduces the production of NO and ROS in LPS-induced RAW264.7 cells. Additionally, it shows substantial protective effects against LPS-induced acute lung injury in mice [1] [2].

Anti-inflammatory agent 17 an orally active anti-inflammatory agent, demonstrates potent efficacy in inhibiting the release of IL-6 and TNF-α without causing cytotoxicity in in vitro experiments. Furthermore, in vivo studies confirm its anti-inflammatory activity. Given its attributes, Compound 17 holds promise for investigating Acute lung injury (ALI) [1].

LYRM03 is an aminopeptidase inhibitor. LYRM03 is also an ubenimex derivative. LYRM03 attenuates LPS-induced acute lung injury in mice by suppressing the TLR4 signaling pathway. LYRM03 effectively attenuates LPS-induced ALI by inhibiting the expression of pro-inflammatory mediators and Myd88-dependent TLR4 signaling pathways in alveolar macrophages. LYRM03 may serve as a potential treatment for sepsis-mediated lung injuries.

Mogroside III-E, a cucurbitane-type compound isolated from Siraitia grosvenorii, exhibits anti-inflammatory activity by attenuating LPS-induced acute lung injury in mice through the regulation of the TLR4 MAPK NF-κB axis via AMPK activation. Additionally, it demonstrates anti-fibrotic activity by reducing pulmonary fibrosis through Toll-Like receptor 4 pathways.

Physalin B is one of the major active compounds from the Solanaceae family of plants and has a wide range of biological activities for the treatment of inflammatory eczema and herpes, among other diseases.Physalin B ameliorates lipopolysaccharide-induced inflammatory response due to acute lung injury by inhibiting NF-κB and NLRP3 through activation of the PI3K Akt pathway.Physalin B inhibits PDGF-BB-induced VSMC proliferation and migration and phenotypic transformation through activation of the Nrf2 pathway. Physalin B inhibits PDGF-BB-induced VSMC proliferation, migration and phenotypic transformation through activation of the Nrf2 pathway.Physalin B exerts antitumor activity by inhibiting LAP2α-HDAC1-mediated deacetylation of glioma-associated oncogene 1 and hepatic stellate cell activation.

MS-II-124 is an effective and selective NLRP3 inhibitor (IC50=0.12 μM) with anti-inflammatory and immunomodulatory properties, suitable for the study of Acute Lung Injury (ALI) Acute Respiratory Distress Syndrome (ARDS).

NF-κB-IN-12 (compound 3h) is a potent NF-κB inhibitor with an IC50 of 1.02 μM, suitable for research in acute lung injury [1].

SZM-1209 is a potent and specific RIPK1 inhibitor with oral activity, displaying a dissociation constant (Kd) of 85 nM. It demonstrates substantial anti-necroptotic efficacy with an EC50 of 22.4 ± 8.1 nM and possesses therapeutic effects against systemic inflammatory response syndrome (SIRS) and acute lung injury (ALI) [1].

Ac2-26 TFA is an active n-terminal peptide in annexin A1 (AnxA1), which can alleviate acute lung injury caused by ischemia-reperfusion.

Ac2-26 TFA, an active N-terminal peptide of annexin A1 (AnxA1), attenuates ischemia-reperfusion-induced acute lung injury. Ac2-26 also decreases AnxA1 protein expression, inhibits the activation of NF-κB and MAPK pathways in the injured lung tissue.

MJ33 lithium salt is an inhibitor of NADPH oxidase type 2-mediated ROS generation, a fluorinated phospholipid analog that inhibits the phospholipase A2 (PLA2) activity of peroxiredoxin 6 (Prdx6), and is used in the study of acute lung injury.