non-alcoholic steatohepatitis

CP-24879 hydrochloride (CP-24879 HCl), a Δ5D/Δ6D dual-inhibitor, can significantly reduce intracellular lipid accumulation and inflammatory injury in hepatocytes. CP-24879 hydrochloride exhibits superior antisteatotic and anti-inflammatory actions in fat-1 and ω-3-treated hepatocytes.

Resmetirom (MGL-3196) is a THR-β agonist (EC50=0.21 μM), with high selectivity and oral activity. Resmetirom can be used in the research of non-cirrhotic and non-alcoholic steatohepatitis.

Selvigaltin (GB1211) is an orally administered, highly selective small-molecule inhibitor of galectin-3 (Gal-3) with an IC₅₀ value of 12 nM in rabbits, exhibiting anticancer and anti-fibrotic activity. Selvigaltin reduces galectin-3 levels in the liver and decreases biomarkers of inflammation (cellular foci) and fibrosis (PSR, SHG), while simultaneously lowering the mRNA and protein expression of inflammatory and fibrotic biomarkers (IL-6, TGF-β3, SNAI2, collagen). Selvigaltin also restores T-cell activity and reduces tumor growth and metastasis. Selvigaltin is suitable for use in studies of liver fibrosis, non-alcoholic steatohepatitis (NASH), and tumors.

Omaveloxolone (RTA-408) is an oral, potent, and selective activator of the nuclear factor erythropoietin-related factor 2 (Nrf2) pathway, as well as a low-potency PPARγ agonist. Omaveloxolone inhibits osteoclast formation by suppressing the STING-dependent NF-κB signaling pathway. Omaveloxolone is being investigated for use in ALS, multiple sclerosis, non-alcoholic steatohepatitis, neurodegenerative diseases, and oncology research.

INT-767 is a potent farnesoid X receptor (FXR)/TGR5 dual agonist that prevents NASH and promotes visceral adipose brown lipogenesis and mitochondrial function for the study of non-alcoholic steatohepatitis.

Apararenone (MT-3995) is a mineralocorticoid receptor antagonist indicated for the treatment of non-alcoholic steatohepatitis and diabetic nephropathy.

Berberine ursodeoxycholate (HTD1801) is an orally effective hypolipidemic agent, an ionic salt of Berberine and Ursodeoxycholic acid.Berberine ursodeoxycholate has a wide range of metabolic activity and significantly reduces liver fat content. Berberine ursodeoxycholate has been used in studies of hyperlipidemia, non-alcoholic steatohepatitis (NASH) and diabetes.

Nivocasan Intermediate is an intermediate of Nivocasan. Nivocasan (GS-9450) is a pan-caspase inhibitor used in the study of HCV infection and non-alcoholic steatohepatitis.

DB1976 dihydrochloride (DB1976 2HCl) , a transcription factor PU.1 inhibitor with potential anti-inflammatory activity, slowed down inflammation and fibrosis and improved glucose homeostasis and dyslipidemia in mice in in vivo experiments.DB1976 dihydrochloride promotes apoptosis and may be used in studies of metabolic dysfunction and non-alcoholic steatohepatitis.

Volixibat is a highly selective and competitive apical sodium-dependent bile acid transporter inhibitor. Volixibat has the potential for treatment for non-alcoholic steatohepatitis.

HPG1860 is a farnesol X receptor (FXR) agonist that effectively activates FXR-mediated transcriptional activity, with an EC50 value of 18 nM. In vivo studies have shown that HPG1860, administered at doses of 1, 3 or 10 mg/kg daily, reduces serum alanine aminotransferase (ALT) and total cholesterol levels in mouse models of non-alcoholic steatohepatitis (NASH) induced by a high-fat diet and carbon tetrachloride (CCl₄). HPG1860 also reduces levels of liver inflammation, lipid accumulation and fibrosis. Consequently, HPG1860 is suitable for research into metabolic diseases, liver fibrosis, bile acid signalling and FXR-mediated transcriptional regulation.

LH10 is an FXR agonist based on fexaramine, with an EC50 of 0.14 μM. It offers hepatoprotective effects, mitigating conditions such as cholestasis induced by alpha naphthylisothiocyanate (ANIT), acute liver injury caused by APAP, and non-alcoholic steatohepatitis (NASH).

GLP-1 receptoragonist 16 (Example 53) is a GLP-1 agonist applicable for research in diabetes, obesity, or diseases related to non-alcoholic steatohepatitis.

NLRP3-IN-70 (Compound 5m) is an inhibitor of the NLRP3 inflammasome with low oral bioavailability. It binds directly to the NACHT domain of the NLRP3 protein, thereby blocking its interaction with ASC, which inhibits ASC oligomerization and the assembly of the NLRP3 inflammasome. NLRP3-IN-70 is applicable in studies on sepsis and non-alcoholic steatohepatitis.

THR-β agonist 2 diacetate (Compound 3) is a potent THR-β agonist with potential applications in researching metabolic disorders such as obesity, hyperlipidemia, hypercholesterolemia, and diabetes, as well as other conditions like steatosis and non-alcoholic steatohepatitis (NASH), atherosclerosis, and other related diseases and conditions.

Linafexor (CS-0159) is a non-steroidal FXR (farnesoid X receptor) agonist for studying primary sclerosing cholangitis (PSC) and non-alcoholic steatohepatitis (NASH).

GLP-1R modulator-1 (Compound 384) is a potent and orally active selective agonist of the glucagon-like peptide-1 receptor (GLP-1R). It activates G protein-coupled signaling, leading to increased intracellular cAMP levels, enhanced insulin secretion, delayed gastric emptying, and reduced appetite. GLP-1R modulator-1 holds potential for research in type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH).

ACC-IN-1 (Compound B1) is an allosteric inhibitor of acetyl-CoA carboxylase (ACC). It targets ACC to regulate lipid metabolism, potentially improving liver steatosis and inflammation associated with non-alcoholic steatohepatitis (NASH).

HSD17B13-IN-105 (Compound EX.87) is a selective inhibitor of 17β-hydroxysteroid dehydrogenase 13 (17BHSD13) with an IC50 value of 0.036 μM, demonstrating high selectivity over 17BHSD4, which has an IC50 value of 31.5 μM. HSD17B13-IN-105 shows potential for research in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

TBPH exacerbates liver steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) mouse models. It induces phospholipid metabolism disorders, reducing cardiolipin (CL) and phosphatidylserine (PS) levels. TBPH impairs endoplasmic reticulum-mitochondria (ER-Mito) contact, leading to mitochondrial dysfunction. Additionally, TBPH causes lung injury through mitochondrial-derived ds-DNA-mediated inflammatory responses. TBPH is utilized to study the role of MFN2-mediated ER-Mito contact in lipid metabolism homeostasis.

GLP-1R agonist 34 (Compound 1) is an orally active small molecule agonist of the glucagon-like peptide-1 receptor (GLP-1R). It enhances insulin secretion, suppresses glucagon release, and slows gastric emptying, thereby effectively reducing blood glucose levels. GLP-1R agonist 34 holds potential for research into metabolic disorders such as type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH).

MPO-IN-9 is a specific myeloperoxidase (MPO) inhibitor with an IC50 value of 3.9 nM. It suppresses MPO-mediated ROS production and safeguards NO-dependent vascular functions by obstructing the chlorination and peroxidase cycles of MPO. MPO-IN-9 has potential applications in researching diseases such as chronic kidney disease and non-alcoholic steatohepatitis.

TBPH is a brominated flame retardant that exacerbates hepatic steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) mouse models. It disrupts phospholipid metabolism, reducing levels of cardiolipin (CL) and phosphatidylserine (PS). TBPH impairs endoplasmic reticulum-mitochondria (ER-Mito) contact, leading to mitochondrial dysfunction. Additionally, TBPH induces lung injury through a mitochondrial-derived ds-DNA mediated inflammatory response. It is also used to investigate the role of MFN2-mediated ER-Mito contact in lipid metabolism homeostasis.

SLC6A19-IN-2 (Example 4) is a potent inhibitor of SLC6A19 with an IC50 of 14 nM. This compound is applicable in the study of metabolic disorders, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), and phenylketonuria (PKU).