lung injury

L48H37 is a chemically stable analog of Curcumin. It exhibits potent inhibitory properties against myeloid differentiation protein 2 (MD2), acting as a specific inhibitor. Its mechanism involves inhibiting the interaction and signaling transduction of LPS-TLR4/MD2. L48H37 is primarily utilized in sepsis and lung injury research [1].

Aviptadil Acetate (Vasoactive Intestinal Peptide acetate salt) induces pulmonary vasodilation and inhibits the proliferation of vascular SMCs and platelet aggregation. Avitadil acetate can be used for research on pulmonary fibrosis, pulmonary hypertension (PAH), and respiratory failure caused by SARS-CoV-2.

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

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.

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.

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.

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

1. Linalool (Linalol), a natural compound of the essential oils, has been shown to have antinociceptive, antimicrobial, and anti-inflammatory properties. 2. Linalool was protected against LPS/GalN-induced liver injury through induction of antioxidant defense via Nrf2 activating and reduction inflammatory response via NF-κB inhibition. 3. Linalool biosynthesis and accumulation might be involved in plant defense against bacterial and fungal pathogens and be associated with field resistance to citrus canker. 4. Linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6.

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.

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

SN50 is a cell permeable NF-κB translocation inhibitor.

FTY720 (S)-Phosphate is the active stereoisomeric phosphate derivative of FTY720 that acts as a potent modulator of sphingosine-1-phosphate (S1P) receptors. FTY720 (S)-Phosphate binds to S1P receptor subtypes S1P1, S1P3, S1P4, and S1P5 with Ki values of 2.1, 5.9, 23, and 2.2 nM respectively, causing receptor internalization on lymphocytes， preventing S1P-mediated lymphocyte egress from lymphoid tissues. FTY720 (S)-Phosphate also enhances endothelial barrier integrity, stimulates transporters such as Abcb1 and Abcc1, and inhibits cytosolic phospholipase A2 activity, highlighting its multifunctional pharmacological properties, making it an compound of interest in the research of diseases including multiple sclerosis, autoimmune diseases and cancer.

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

NLRP3-IN-45 (D6) serves as an inhibitor specifically targeting the NLRP3 inflammasome, demonstrated through its ability to curb the activity of IL-1β (IC 50 = 41.79 nM). It effectively prevents the activation of the NLRP3 inflammasome while sparing the initial stages of its activation process. Furthermore, NLRP3-IN-45 has been shown to selectively inhibit NLRP3 inflammasome activation in the LPS-induced acute lung injury (ALI) mouse model.

Keap1-Nrf2-IN-22 (compound 19) acts as a Keap1-Nrf2 inhibitor with a KD2 value of 42.2 nM. It is utilized in research focused on acute lung injury (ALI) and cerebral ischemia/reperfusion (I/R) injuries.

GPD-1116 is an orally active inhibitor of phosphodiesterase (PDE)4 and PDE1. The compound effectively reduces smoke-induced apoptosis in lung cells. Additionally, GPD-1116 has shown efficacy in various animal disease models, including emphysema, acute lung injury, chronic obstructive pulmonary disease (COPD), asthma, and pulmonary arterial hypertension.

TH023 is an inhibitor of the TLR4 signaling pathway, specifically targeting the formation of TLR4 homodimers. In HEK-Blue hTLR4 cells, TH023 suppresses the secretion of embryonic alkaline phosphatase with an IC50 of 0.354 μM and inhibits NO expression in RAW264.7 cells, with an IC50 of 1.61 μM. Additionally, TH023 inhibits the activation of NF-κB and reduces the nuclear translocation of NF-κB p65. The compound demonstrates anti-inflammatory effects in a mouse model of LPS-induced acute sepsis and improves lung injury in mice.

Nrf2 activator 18 (Compound 11a) is an orally active activator of the Keap1/Nrf2/HO-1 signaling pathway, promoting Nrf2 nuclear translocation and enhancing antioxidant effects. It inhibits IL-6 release with an IC50 of 4.816 μM. In a mouse model of PM2.5-induced lung injury, Nrf2 activator 18 demonstrates anti-inflammatory activity.

IL-6-IN-1 (Compound 22) inhibits the release of IL-6 with an IC50 of 1.065 μM and demonstrates anti-inflammatory activity in LPS-induced acute lung injury in mice.

MyD88-IN-2 (compound A5S) is a MyD88 inhibitor with a Kd value of 15 μM. It demonstrates protective effects in mouse models of acute lung injury induced by LPS and sepsis.

DualCathepsinL/JAK-IN-1 (Compound A8) serves as a dual inhibitor of Cathepsin L (CTSL) and JAK, exhibiting IC50 values of 0.68 μM for CTSL and 337.1 nM, 5.251 nM, 27.29 nM, and 172.6 nM for JAK1/2/3 and TYK2, respectively. This compound effectively prevents the activation of MAPK, NF-κB, and JAK/STAT signaling pathways, leading to significant anti-inflammatory therapeutic effects. DualCathepsinL/JAK-IN-1 is applicable in research on acute lung injury (ALI).

P2Y14R antagonist 3 (compound A) is an orally active P2Y14R antagonist with an IC50 of 23.60 nM and a Kd of 7.26 μM. It mitigates lung injury in mice induced by Lipopolysaccharides (LPS) and can be utilized in the study of inflammatory diseases.

PDE4-IN-26 (Compound A5) is an orally active, highly selective inhibitor of PDE4. It exhibits anti-inflammatory properties by inhibiting p38 MAPK phosphorylation. In mouse models of acute lung injury and chronic obstructive pulmonary disease, PDE4-IN-26 reduces lung inflammation, damage, and fibrosis, while promoting sputum secretion and alleviating cough. It is useful for researching lung injury-related diseases.