non-alcoholic

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.

H-Asp(OtBu)-OtBu HCl is an aspartic acid derivative that may be used to study comparative neurological function and metabolic disorders of non-alcoholic hepatitis.

Vidofludimus (SC12267) (4SC-101, SC12267) is a novel small molecule inhibitor of dihydroorotate dehydrogenase (DHODH).

Glycolithocholic acid (Lithocholic acid glycine conjugate) is a glycine conjugate of lithocholic acid.

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.

GOAT-IN-1 is an inhibitor of ghrelin O-acyltransferase (GOAT) that may be useful for the prophylaxis or treatment of diabetes, hyperlipidemia, non-alcoholic fatty liver, Alzheimer's disease, Parkinson's disease, cerebrovascular dementia, and cerebral infarction.

PTUPB is a potent dual inhibitor of sEH and COX-2 enzymes with IC50 values of 0.9 nM and 1.26 μM, respectively.

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

PCSK9-IN-29 serves as a lipid-lowering agent that enhances the expression of low-density lipoprotein receptor (LDLR) protein and reduces PCSK9 protein expression in hepG2 cells. Additionally, in crab-eating macaques on a high-fat diet, it lowers serum LDL-C, TC, and liver enzyme ALT levels, reduces body weight and fat, and boosts bone mineral content. PCSK9-IN-29 is useful for studies involving non-alcoholic fatty liver disease and obesity.

HPG1860, an agonist of the farnesoid X receptor (FXR), induces luminescence in reporter gene assays utilizing HEK293T cells expressing human FXR, with an EC50 value of 18 nM. In vivo studies demonstrate that HPG1860 (administered at 1, 3, or 10 mg kg daily) reduces serum alanine aminotransferase (ALT) and total cholesterol levels in a mouse model of non-alcoholic steatohepatitis (NASH), which was induced by a high-fat diet and carbon tetrachloride (CCl4). Additionally, this compound decreases hepatic inflammation, fat levels, and fibrosis.

SET-171 is a JNK (c-Jun N-terminal kinase) inhibitor that exhibits significant anticancer activity by suppressing the expression of hepatic pyruvate kinase (PKL) and offers potential in regulating lipid metabolism. In antitumor studies, SET-171 shows notable cytotoxicity against human liver cancer cell lines HepG2 and Huh7, with IC50 values of 8.82 μM and 2.97 μM, respectively. Additionally, in research related to non-alcoholic fatty liver disease (NAFLD), SET-171 significantly reduces triglyceride (TAG) levels and inhibits the expression of proteins associated with steatosis. This compound holds promise for hepatocellular carcinoma (HCC) and NAFLD research.

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.

SKLB102 exhibits high affinity for PPARγ. It has a potent ability to reduce fat deposition and protect the liver from non-alcoholic fatty liver disease (NAFLD) by regulating adipokine expression and preventing insulin resistance.

PPARγ-IN-5 (Compound A3) is an inhibitor of PPARγ. In liver cells, it reduces lipid accumulation and shows no significant cytotoxicity in HepG2 cells at a concentration of 400 µM. PPARγ-IN-5 is applicable for research on non-alcoholic fatty liver disease.

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.

p-nitro-Pifithrin-α is a cell-permeable analog of pifithrin-α, a potent p53 inhibitor. It suppresses p53-mediated TGF-β1 expression in HK-2 cells and inhibits the activation of caspase-3 by Zika virus (ZIKV) strains. Moreover, p-nitro-Pifithrin-α attenuates steatosis and liver injury in mice subjected to a high-fat diet, mitigating the effects of non-alcoholic fatty liver disease [1] [2] [3] [4].

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.

Leucocyanidin (Leucocianidol) is an antiulcer compound extracted from Aesculus Hippocastanum Seeds. Leucocyanidin can be used to study non-alcoholic fatty liver disease.

1-Palmitoyl-2-stearoyl-3-oleoyl-rac-glycerol is a triacylglycerol that contains palmitic , stearic , and oleic acid at the sn-1, sn-2, and sn-3 positions, respectively. It has been detected in RAW 264.7 cells by neutral loss MS. Increased serum levels of 1-palmitoyl-2-stearoyl-3-oleoyl-rac-glycerol are a potential biomarker for non-alcoholic fatty liver disease (NAFLD).

Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities, including antibacterial, anticancer, antiplatelet, and antioxidant properties.1,2,3,4It is active against Gram-positive (MICs = 5-160 µg/ml) and Gram-negative bacteria (MICs = 136-200 µg/ml), as well as yeasts (MICs = 10-20 µg/ml).1Ajoene is cytotoxic to mouse melanoma cells (IC50= 18 µM), as well as human colon, lung, mammary, and pancreatic cancer cells (IC50s = 7-41 µM).2It reduces tumor growth in a B16/BL6 mouse model of melanoma when administered at a dose of 25 mg/kg every other day and decreases the number of lung metastases when administered prior to tumor cell inoculation at doses ranging from 1-25 mg/kg. It inhibits ADP- or collagen-induced platelet aggregation in isolated baboon platelets when used at concentrations ranging from 75 to 150 µg/ml and in platelet-rich plasma isolated from baboons when administered at a dose of 25 mg/kg.3Ajoene (25 mg/kg) prevents thrombus formation on damaged arterial walls in heparinized pigs in anin situmodel of thrombogenesis.5It also reduces high-fat diet-induced hepatic steatosis, histopathological markers of liver damage, thiobarbituric acid reactive substances (TBARS) formation, and protein oxidation in a mouse model of non-alcoholic fatty liver disease (NAFLD).4 1.Naganawa, R., Iwata, N., Ishikawa, K., et al.Inhibition of microbial growth by ajoene, a sulfur-containing compound derived from garlicAppl. Environ. Microbiol.62(11)4238-4242(1996) 2.Taylor, P., Noriega, R., Farah, C., et al.Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 miceCancer Lett.239(2)298-304(2006) 3.Teranishi, K., Apitz-Castro, R., Robson, S.C., et al.Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic derivative, ajoeneXenotransplantation10(4)374-379(2003) 4.Han, C.Y., Ki, S.H., Kim, Y.W., et al.Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activationAntioxid. Redox Signal.14(2)187-202(2011) 5.Apitz-Castro, R., Badimon, J.J., and Badimon, L.A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental modelThromb. Res.75(3)243-249(1994)

SHS4121705 is an orally bioavailable mitochondrial uncoupler.1It increases oxygen consumption rate in L6 rat myoblast cells with an EC50value of 4.3 μM. SHS4121705 (25 mg/kg per day in the diet) reduces hepatic steatosis, liver triglyceride levels, and plasma alanine aminotransferase (ALT) levels in Stelic animal model (STAM) mice, a model of non-alcoholic steatohepatitis (NASH). 1.Salamoun, J.M., Garcia, C.J., Hargett, S.R., et al.6-Amino[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol derivatives as efficacious mitochondrial uncouplers in STAM mouse model of nonalcoholic steatohepatitisJ. Med. Chem.63(11)6203-6224(2020)