liver fibrosis

SEW 2871 is an orally available, highly selective S1P1 agonist with an EC50 of 13.8 nM.It reduces the number of lymphocytes in the blood and is used in studies related to diabetes, Alzheimer's disease, liver fibrosis, and inflammation. It activates ERK, Akt and Rac signaling pathways and induces S1P1 internalization and recycling.

Enoxaparin sodium is a low-molecular-weight heparin (LMWH) that has recently been approved by the US FDA for use in patients with medically managed ST-segment myocardial infarction (STEMI), or STEMI with subsequent percutaneous coronary intervention (PCI)

Icosabutate (NST-4016) is an orally active derivative of eicosapentaenoic acid that inhibits hepatic inflammation and fibrosis in NASH, improves cardiovascular risk profiles in statin-treated patients with residual hypertriglyceridemia, lowers triglycerides, and may be useful in studies of liver fibrosis and atherosclerosis.

safironil is a novel antifibrotic compound and a competitive inhibitor of collagen synthesis. safironil inhibited in vitro experiments on fibroblast activation monitored by collagen I mRNA or smooth muscle alpha-actin levels, and fibrogenesis as judged by type I and type III collagen and laminin production. safironil had no effect on the size of liver granulomas without altering total hydroxyproline, but altered the pattern of fibrosis by increasing type III and decreasing type I collagen deposition.

Thioacetamide (TAA) is an indirect hepatotoxin commonly used to induce experimental liver injury. It is metabolized by CYP2E1 into reactive metabolites that covalently bind to proteins and lipids, leading to oxidative stress and centrilobular necrosis, hepatocyte death, and M1 M2 macrophage-dominated inflammation. TAA is widely used to establish models of chronic liver fibrosis, hepatic encephalopathy, and liver cancer.

Sinapinic Acid (Synapoic acid) protects the rat liver from CCl4-induced inflammation, most likely by acting as a free radical scavenger and modulator of NF-κB p65 activation and proinflammatory cytokine expression. Sinapic acid with antioxidant role protects cardiac cells and its functions from I/R induced oxidative stress. Sinapic acid is a potentially useful agent for the protection against liver fibrosis and cirrhosis. Sinapic acid prevents the alterations in the levels of lipids and lipoproteins by virtue of its anti-lipidaemic effect in isoproterenol induced myocardial infarcted rats. Sinapic acid ameliorates hyperglycemia through PLC-PKC signals to enhance the glucose utilization in diabetic rats.

1. Berberine (Umbellatine) is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism. 2. Berberine may as a broad-spectrum anti-microbial medicine, a complementary therapeutic agent for HIV/AIDS. 3. Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders. 4. Berberine is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 7516. 5. Berberine reduces hepatic fat content in rats with nonalcoholic fatty liver disease; also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury. 6. Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states. 7. Berberine has antineoplastic effects, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma, etc.

4-Hydroxypyrrolidine-2-carboxylic acid (4-hydroxyproline) is a non-protein amino acid and endogenous metabolite present in collagen that modulates collagen elasticity and can be used as a diagnostic marker for bone conversion and liver fibrosis.

1. Betulonic acid (Liquidambaric acid) amide stimulated the regenerative response in hepatocytes under conditions of combined toxic exposure and promoted recovery of their qualitative and quantitative characteristics, which was accompanied by a significant decrease in the severity of liver fibrosis and the absence of cirrhotic transformation of the liver. 2. Betulonic acid derivatives have a promising cytostatic activity in vitro and could be used as potential leads for the development of new type of anti-cancer agents. 3. Betulonic acid has antiholestatic effects in mice.

TAT-Gap19 acetate is a specific inhibitor of connexin43 hemichannel (Cx43 HC). TAT-Gap19 acetate traverses the blood-brain barrier and alleviates liver fibrosis in mice. TAT-Gap19 acetate does not inhibit the corresponding Cx43 GJCs.

Fezagepras (Setogepram) is an orally active GPR40 agonist and is an antagonist or inverse agonist of GPR84 with anti-inflammatory, anti-fibrotic, and anti-proliferative actions.

BAR-2227 (compound 3a) functions as an FXR agonist and a LIFR inhibitor. It is utilized in the study of liver fibrosis and inflammation.

Anti-NASH agent 2 (compound 21) is an inhibitor of neolipogenesis activity and α-SMA gene expression. It improves hepatic steatosis, edema, inflammatory infiltration, and liver fibrosis in NASH mouse models.

VDR agonist 3 (Compound E15) is a potent activator of the vitamin D receptor (VDR). It effectively inhibits the activation of hepatic stellate cells (HSC) via VDR. In a model of liver fibrosis induced by CCl4 in mice, VDR agonist 3 significantly alleviates liver fibrosis without causing hypercalcemia.

METTL3activator-1 (2-Piperazinecarboxylic acid methyl ester dihydrochloride) is an activator of Mettl3, enhancing its expression, and is useful in liver fibrosis research.

FGFRs-IN-1 (Compound A16) is an orally active inhibitor targeting FGFR1 2 3 4, with IC50 values of 2.3, 7, 11, and 163 nM respectively. It also inhibits VEGFR1 2 3, Abl, and Flt3, with IC50 values of 61, 176, 112, 26, and 353 nM. The compound shows weak inhibition of CYP enzymes. FGFRs-IN-1 reduces the expression of α-SMA and collagen I, and it inhibits epithelial-mesenchymal transition (EMT) in A549 cells stimulated by TGF-β1. Additionally, FGFRs-IN-1 demonstrates anti-inflammatory activity in mouse models of lung fibrosis induced by Bleomycin and liver fibrosis induced by CCl4.

FXR agonist12 (Compound C7) is an orally active FXR agonist. It downregulates bile acid synthesis-related genes and upregulates bile acid transport-related genes in HepG2 cells. FXR agonist12 alleviates ANIT-induced cholestasis and reduces liver damage and fibrosis in a mouse model of NASH.

Hydroxy tipelukast (Compound MN-002), a metabolite of Compound MN-001, is an orally active phenoxyalkyl carboxylic acid. It inhibits hepatic steatosis, lobular inflammation, hepatocellular ballooning, and liver fibrosis, while also reducing hepatic hydroxyproline levels. Hydroxy tipelukast is a promising candidate for the study of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

5-HT2B antagonist-2 (Compound 19c) is a 5HT2B receptor antagonist with an IC50 of 1.09 nM. It effectively downregulates the expression of fibrosis-related genes α-SMA, Timp1, Col1a1, and Col3a1, significantly reducing cellulose deposition. In a CCl4-induced liver fibrosis mouse model, it decreases the fibrotic area and inhibits the progression of fibrosis. This compound is useful for research into immune-inflammatory related diseases, particularly pulmonary fibrosis.

Galectin-3-IN-6 (Compound 12) is an orally active galectin-3 (Gal-3) inhibitor, with an IC50 of 12 nM and a Kd of 13 nM for Gal-3. In a CCl4-induced mouse model of acute liver injury and fibrosis, Galectin-3-IN-6 significantly reduces fibrosis markers collagen-1 and α-smooth muscle actin (αSMA) by 64% and 71%, respectively, demonstrating notable anti-fibrotic activity. Galectin-3-IN-6 is applicable for research in fibrosis-related diseases, cancer, and cardiovascular disorders.

KYLO-0603 is an orally active and selective THR-β agonist with an EC50 of 31.07 nM. It effectively reduces serum cholesterol and low-density lipoprotein cholesterol levels. By activating THR-β receptors, KYLO-0603 enhances the expression of THR-regulated genes like iodothyronine deiodinase 1 (Dio1), malic enzyme 1 (Me1), and thyroid hormone-responsive (Thrsp) gene, while it inhibits the expression of inflammatory and fibrosis-related genes, including low-density lipoprotein receptor (LDL-R) gene. This compound is applicable for the study of metabolic associated steatohepatitis (MASH) and liver fibrosis.

CypB-IN-1 (Compound 11) is an inhibitor of cyclophilin B (CypB) with a dissociation constant (Kd) of 12 nM. It is used in research related to metabolic dysfunction-associated steatohepatitis (MASH) and the liver fibrosis diseases it induces.

NF-κB/HIF-1α-IN-1 (compound 9c) effectively inhibits the NF-κB activation pathway and demonstrates selective antifibrotic activity. This compound exhibits no significant cytotoxicity in NCI tumor cell lines. In rat models, NF-κB/HIF-1α-IN-1 successfully ameliorates liver fibrosis, suppresses the expression levels of NF-κB and HIF-1α, and induces Nrf2.

Anti-inflammatory agent 101 (Compound C04) is an orally active anti-inflammatory agent with notable anti-lipid accumulation, anti-inflammatory, and anti-fibrotic properties. It functions by reducing fatty acid uptake, enhancing fatty acid oxidation, and alleviating inflammation, making it applicable in the study of NASH and related liver fibrosis.