lung fibrosis

3-CPs (3-Carbethoxypsoralen) is a bleomycin-induced serotypic podoplanar polysaccharide in mouse lung fibrosis that belongs to the psoralen family and interferes with antibody-mediated bacterial killing.3-CPs delays bleomycin-induced lung fibrosis in mice and can be used in studies of airway inflammation and asthma.

1. Peiminine (Raddeanine) is an effective inhibitor for lung inflammation and pulmonary fibrosis in a rat model of bleomycin-induced lung injury.

Lonidamine (Diclondazolic Acid) is an indazole carboxylic acid derivative, principally inhibiting aerobic glycolytic activity, by its effect on mitochondrially-bound hexokinase (HK).

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.

ATUX-1215, a protein phosphatase 2A (PP2A) activator, diminishes the phosphorylation of ERK, p38, JNK, and Akt, as well as decreases the secretion of IL-12p70, GM-CSF, and IL1α in BLM-treated animals, potentially decelerating lung fibrosis progression [1].

GK444 (Compound 15a), a selective HDAC1/2 inhibitor with IC50 values of 100 nM and 92 nM for HDAC1 and HDAC2 respectively, demonstrates an IC50 of 4.1 μM in Caco-2 cell inhibition. Additionally, GK444 attenuates TGF-β1-induced COL1A1 mRNA expression in primary normal human lung fibroblasts and mitigates Bleomycin-induced lung fibrosis in mice [1].

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

PAT-048 is an effective and selective autotaxin inhibitor. PAT-048 reduces dermal fibrosis in vivo. PAT-048 also inhibits IL-6 mRNA expression but displays no effect on autotaxin protein and pulmonary lysophosphatidic acid (LPA) production in the lung fibrosis model. PAT-048 has an IC50 and IC90 of 20 nM and 200 nM for autotaxin in mouse plasma.

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.

Camostat, also known as FOY 305, is a serine protease inhibitor. Camostat is used in the treatment of some forms of cancer and is also effective against some viral infections, as well as inhibiting fibrosis in liver or kidney disease or pancreatitis. It is an inhibitor of the enzyme transmembrane protease, serine 2 (TMPRSS2). Inhibition of TMPRSS2 partially blocked infection by SARS-CoV and Human coronavirus NL63 in HeLa cell cultures. In vitro study showed that camostat significantly reduces the infection of Calu-3 lung cells by SARS-CoV-2, the virus responsible for COVID-19.

Galectin-3/galectin-8-IN-1 (Compound 53) serves as a dual inhibitor of the Galectin-3 and galectin-8 C-terminal domains, exhibiting dissociation constants (Kd) of 4.12 μM for Galectin-3 and 6.04 μM for galectin-8. It effectively impedes the migration of MRC-5 lung fibroblast cells and is utilized in cancer and tissue fibrosis research [1].

Rupatadine (UR-12592) is a potent dual PAF/H1 antagonist with Ki of 0.55/0.1 uM(rabbit platelet membranes/guinea pig cerebellum membranes).IC50 value:Target: PAF/H1 antagonistin vitro: Rupatadine competitively inhibited histamine-induced guinea pig ileum contraction (pA2 = 9.29 +/- 0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4 (LTD4). It also competitively inhibited PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2 = 6.68 +/- 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 microM), while not affecting ADP- or arachidonic acid-induced platelet aggregation [1]. The IC50 for rupatadine in A23187, concanavalin A and anti-IgE induced histamine release was 0.7+/-0.4 microM, 3.2+/-0.7 microM and 1.5+/-0.4 microM, respectively whereas for loratadine the IC50 was 2.1+/-0.9 microM, 4.0+/-1.3 M and 1.7+/-0.5 microM. SR-27417A exhibited no inhibitory effect [2].in vivo: Rupatadine blocked histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 micrograms/kg i.v.). Moreover, it potently inhibited PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.) [1]. rupatadine treatment improved the declined lung function and significantly decreased animal death. Moreover, rupatadine was able not only to attenuate silica-induced silicosis but also to produce a superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist loratadine, or PAF antagonist CV-3988 [3]. [1]. Merlos M, et al. Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF). J Pharmacol Exp Ther. 1997 Jan;280(1):114-21. [2]. Queralt M, et al. In vitro inhibitory effect of rupatadine on histamine and TNF-alpha release from dispersed canine skin mast cells and the human mast cell line HMC-1. Inflamm Res. 2000 Jul;49(7):355-60. [3]. Lv XX, et al. Rupatadine protects against pulmonary fibrosis by attenuating PAF-mediated senescence in rodents. PLoS One. 2013 Jul 15;8(7):e68631.

1. Ecliptasaponin A (Echinocystic acid-3-o-glucoside) has protective effects against the pulmonary fibrosis induced by bleomycin via reducing the oxidative stress, lung tissue inflammation, and the subsequent epithelial-mesenchymal transition.

JNK-1-IN-2 (Compound c6) is a potent inhibitor of JNK-1 with an IC50 of 33.5 nM, and also exhibits inhibitory effects on JNK-2 and JNK-3 with IC50 values of 112.9 nM and 33.2 nM, respectively. This compound effectively inhibits the phosphorylation of c-Jun and has shown potential in reversing lung impairment, making it relevant for research into pulmonary fibrosis [1].

PDE1-IN-4 is a potent and selective inhibitor of PDE1 (phosphodiesterase-1), acting on PDE1C (IC50: 10 nM), PDE1A (IC50: 145 nM) and PDE1B (IC50: 354 nM). PDE1-IN-4 regulates cAMP (3′,5′-cyclic adenosine monophosphate) and cGMP (3′,5′-cyclic guanosine monophosphate) and exhibits antifibrotic effects. PDE1-IN-4 can inhibit TGF-β1-induced differentiation of human lung fibroblasts, and can be used to study idiopathic pulmonary fibrosis (IPF).

ATX inhibitor 15 (compound 30) is an indole-based carbamate derivative with a strong inhibitory effect on autotaxin (ATX), demonstrated by an IC50 of 2.17 nM. Additionally, ATX inhibitor 15 effectively inhibits ATX activity in vivo and suppresses the expression of pro-fibrotic genes. Furthermore, ATX inhibitor 15 exhibits protective effects in lung fibrosis induced by Bleomycin in mice [1].

Bexotegrast, also known as PLN-74809, is a small-molecule, dual selective inhibitor of αVβ1 / αVβ6 for idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis (PSC). These integrins cause upstream activation of TGF-β1 in actively fibrotic tissue. Inhibition of these integrins will block TGF-β1 activation, thereby preventing the growth of fibrotic tissue within the lung and bile ducts.

ATX inhibitor 11 is a potent inhibitor of ATX (autotaxin) (IC50: 2.7 nM). ATX inhibitor 11 alleviates the severity of fibrotic tissue and effectively reduces the deposition of α-SMA, a biomarker of fibrosis, in a mouse model of fibrosis. ATX inhibitor 11 can be used to study lung fibrosis.

Mogroside III-E is a cucurbitane-type compound isolated from Siraitia grosvenorii, has anti-inflammatory activity, it attenuates LPS-induced acute lung injury in mice partly through regulation of the TLR4/MAPK/NF-κB axis via AMPK activation. It also has anti-fibrotic activity, it reduces pulmonary fibrosis through Toll-Like receptor 4 pathways.

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

Galectin-3/galectin-8-IN-2 (Compound 57) is a dual inhibitor targeting the C-terminal domains of Galectin-3 and galectin-8, exhibiting dissociation constants (Kd) of 12.8 μM and 2.06 μM, respectively. It effectively inhibits the migration of MRC-5 lung fibroblast cells and serves as a potential research tool for studying cancer and tissue fibrosis [1].

1-Thioglycerol, widely utilized as a reducing agent in protein chemistry and molecular biology, serves to safeguard proteins against oxidation and denaturation by reducing disulfide bonds to their thiol bases for subsequent modification or analysis. Additionally, its exploration in medical applications comprises its potential as a cystic fibrosis inhibitor to enhance lung cell function. It also finds application in the preparation of metal nanoparticles and as a stabilizer in specific pharmaceutical formulations.

LasR-IN-2, a compound that inhibits the activity of LasR, forms hydrogen bonding with the TRY-56 residue. It finds application in the study of bacterial infection, neutropenia, severe burns, and chronic lung disease in cystic fibrosis (CF) [1].

GTS-21 dihydrochloride (DMBX-anabaseine) is a nAChRs agonist. nAChRs are neuron receptor proteins that activated by the binding of the neurotransmitter ACh.

Aviptadil (INN) is an analog of vasoactive intestinal polypeptide (VIP) for the treatment of erectile dysfunction.