non-alcoholic

CX08005 is a protein tyrosine phosphatase 1B inhibitor. CX08005 reduces hepatic lipid accumulation and microcirculatory impairment associated with non-alcoholic fatty liver disease.

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.

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.

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

ZLY032 is a dual agonist of free fatty acid receptor 1 (FFAR1/GPR40; EC50= 68 nM in a FLIPR assay) and peroxisome proliferator-activated receptor δ (PPARδ; EC50= 102 nM in a reporter assay).1It is selective for FFAR1 and PPARδ over PPARα and PPARγ (EC50s = >10 μM for both). ZLY032 (40 mg/kg, twice per day) reduces blood glucose levels in an oral glucose tolerance test and decreases plasma total cholesterol and triglyceride levels in theob/obmouse model of metabolic disease.2It reduces hepatic steatosis and plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in a mouse model of non-alcoholic steatohepatitis (NASH) induced by a methionine and choline-deficient diet at the same dose. 1.Li, Z., Chen, Y., Zhou, Z., et al.Discovery of first-in-class thiazole-based dual FFA1/PPARδ agonists as potential anti-diabetic agentsEur. J. Med. Chem.164352-365(2019) 2.Li, Z., Zhou, Z., Hu, L., et al.ZLY032, the first-in-class dual FFA1/PPARδ agonist, improves glucolipid metabolism and alleviates hepatic fibrosisPharmacol Res.159105035(2020)

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.

FXR antagonist 1 is a selective, orally active intestinal FXR antagonist with an IC50 value of 2.1 μM. FXR antagonist 1 antagonises intestinal FXR and selectively inhibits intestinal FXR signalling by feedback activation of hepatic FXR. FXR antagonist 1 can improve liver steatosis, inflammation and fibrosis in the NASH (non-alcoholic steatohepatitis) model and can be used to study NASH.

Ervogastat (PF-06865571) is a potent and well-tolerated diacylglycerol acyltransferase 2 inhibitor. Ervogastat reduces steatosis and hepatic triglyceride levels in non-alcoholic steatohepatitis (NASH).

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.

1-Palmitoyl-sn-glycerol 3-phosphate (1-P-GPA), an endogenous metabolite, is used in research on non-alcoholic fatty liver disease [1].

2-Oleoylglycerol is a lipid found in palm kernel, sunflower seed and rice bran.2-Oleoylglycerol acts as a GPR119 agonist with neuroprotective effects and induces secretion of glucagon-like peptide 1 (GLP-1).2-Oleoylglycerol is used in the modelling of non-alcoholic steatohepatitis.

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).

Efruxifermin, an Fc-FGF21 fusion protein consisting of a human IgG1 Fc domain linked to modified human FGF21, exhibits a prolonged half-life and enhanced receptor affinity compared to its native counterpart. It is utilized in researching non-alcoholic steatohepatitis [1].

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)

MBX-8025 is an agonist of peroxisome proliferator-activated receptor δ (PPARδ).1 It is greater than 750- and 2,500-fold selective for PPARδ over PPARα and PPARγ. MBX-8025 (10 mg/kg per day for eight weeks) reduces increases in fasting blood glucose and serum insulin levels, and decreases insulin resistance in Alms1 mutant (foz/foz) mice fed an atherogenic diet as a model of diet-induced obesity, type 2 diabetes, and non-alcoholic steatohepatitis (NASH).2 It also decreases serum alanine transaminase (ALT), as well as serum and hepatic cholesterol and triglyceride, levels and reduces markers of NASH in the same model. |1. Bays, H.E., Schwartz, S., Littlejohn, T., 3rd, et al. MBX-8025, a novel peroxisome proliferator receptor-δ agonist: Lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin. J. Clin. Endocrinol. Metab. 96(9), 2889-2897 (2011).|2. Haczeyni, F., Wang, H., Barn, V., et al. The selective peroxisome proliferator-activated receptor-delta agonist seladelpar reverses nonalcoholic steatohepatitis pathology by abrogating lipotoxicity in diabetic obese mice. Hepatol. Commun. 1(7), 663-674 (2017).

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)

NSC 48160, a chemical compound, exhibits inhibitory effects on pancreatic cancer cell proliferation, with half-maximal inhibitory concentrations (IC50s) of 84.3 μM for CPFAC-1 and 94.5 μM for BxPC-3. It also promotes apoptosis in pancreatic cancer cells. Additionally, NSC 48160 has been shown to ameliorate metabolic syndromes, including non-alcoholic steatohepatitis (NASH), obesity, and lipid metabolism disorders [1] [2].

Glycolithocholic acid sodium salt, the sodium form of Glycolithocholic acid, is a glycine-conjugated secondary bile acid utilized in diagnosing ulcerative colitis (UC), non-alcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC).

Nimacimab is a recombinant humanized monoclonal antibody. It can improve diabetes and non-alcoholic steatohepatitis.

MGAT2-IN-4 (compound 33) is a monoacylglycerol acyltransferase 2 (MGAT2) inhibitor with liver metabolic stability, applicable in obesity, diabetes, and non-alcoholic steatohepatitis (NASH) research [1].

S217879 is a potent and selective activator of NRF2 that disrupts the KEAP1-NRF2 interaction, resulting in significant activation of the NRF2 pathway. This compound is applicable in research on non-alcoholic steatohepatitis (NASH) [1].

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.

PPARα δ agonist 1 is a potent dual agonist with EC50 values of 7.0 nM for PPARα and 8.4 nM for PPARδ, exhibiting high selectivity for PPARγ (EC50: 1316.1 nM). Agonist 1 has potential for non-alcoholic steatohepatitis studies.

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.

Demethyleneberberine chloride, a natural mitochondria-targeted antioxidant, mitigates colitis in mice and suppresses inflammatory responses by blocking the NF-κB pathway and modulating the equilibrium of Th cells. It is also recognized as an AMPK activator for investigating non-alcoholic fatty liver disease (NAFLD) [1] [2] [3].

PF-07247685, a potent BCKDC kinase (BDK) inhibitor (EC 50 = 2.2 nM), enhances the binding between BDK and the BCKDH E2 core subunit to block E1 phosphorylation. BDK regulation is crucial for BCKDH activity, which manages the rate-limiting step in the catabolism of branched-chain amino acids (BCAA). Dysfunctional BCAA metabolism is linked to various cardiometabolic disorders such as heart failure (HF), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and obesity. PF-07247685 has demonstrated an ability to improve cardiometabolic parameters and glucose tolerance in mice [1].

EDP-305, an orally active, potent, and selective agonist of the farnesoid X receptor (FXR), exhibits EC50 values of 34 nM in chimeric FXR within CHO cells and 8 nM in full-length FXR in HEK cells. Demonstrating a potent and consistent antifibrotic effect, EDP-305 is utilized in research related to primary biliary cholangitis (PBC) and non-alcoholic steatohepatitis (NASH).

Leronlimab (PRO 140) is a humanized IgG4 anti-CCR5 monoclonal antibody with both anti-HIV and anti-tumor activity, inhibiting CCR-mediated HIV-1 virus and cancer cell metastasis in mouse tumor models. Leronlimab can be used to study HIV, non-alcoholic steatohepatitis (NASH), and breast cancer.

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

Pemvidutide, a dual GLP-1R/GCGR agonist, significantly lowers body weight, liver fat, and serum lipids, holding promise for non-alcoholic steatohepatitis (NASH) and obesity research [1].

BMS-986172 is an orally active, highly selective inhibitor of MGAT2, with inhibitory concentrations (IC50) of 4.6 nM for human MGAT2 (hMGAT2) and 20 nM for mouse MGAT2 (mMGAT2). It exhibits an in vitro half-life (T1 2) greater than 120 minutes and is known to decrease food intake and body weight. This compound is promising for research in metabolic disorders, including obesity and non-alcoholic steatohepatitis (NASH) [1].

Murideoxycholic Acid alleviates non-alcoholic fatty liver disease by modulating the enterohepatic axis.

3-Epideoxycholic acid (EDCA), a secondary bile acid and an epimer of deoxycholic acid, serves as a steroidal host compound in the enantioselective purification of (2R,3S)-3-methyl-2-pentanol from its racemates via enclathration. Additionally, decreased fecal levels of EDCA have been observed in pediatric patients with non-alcoholic fatty liver disease (NAFLD).

Pemvidutide (TFA), a GLP-1R/GCGR dual agonist, effectively reduces body weight, liver fat, and serum lipid levels, and is utilized in research on non-alcoholic steatohepatitis (NASH) and obesity [1].

PF-07238025, a potent branched-chain ketoacid dehydrogenase kinase (BDK) inhibitor with an EC50 of 19 nM, enhances the stability of the BDK-BCKDH core E2 subunit interaction and inhibits the phosphorylation of the E1 subunit. By modulating BDK, which regulates the phosphorylation of BCKDH, a key enzyme in branched-chain amino acid (BCAA) degradation, PF-07238025 indirectly controls the rate-limiting step in BCAA catabolism. Dysregulated BCAA metabolism is implicated in various cardiometabolic disorders such as heart failure (HF), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and obesity. Notably, PF-07238025 has been shown to ameliorate cardiometabolic endpoints and enhance glucose tolerance in mouse models [1].

ML261 is a inhibitor of hepatic lipid droplets formation with an IC 50 of 69.7 nM. ML261 has research value in non-alcoholic fatty liver disease (NAFLD) and inflammation.

FXR agonist 4 with an EC 50 value of 1.05 μM. FXR agonist 4 effectively improves hyperlipidemia, hepatic steatosis, insulin resistance and hepatic inflammation in DIO mice. FXR agonist 4 can be used for the research of non-alcoholic fatty liver disease (NAFLD) .

QH536 is an effective degrader of HMGCR (EC50: 0.22 μM).QH536 exhibits anti-inflammatory effects and does not have the side effect of inducing intracellular accumulation of cholesterol.QH536 can be used to study cardiovascular disease and non-alcoholic steatohepatitis.

THR-β agonist 4 is a potent THR-β agonist with significant research potential for treating metabolic diseases such as hyperlipidemia, obesity, hypercholesterolemia, diabetes, steatosis, non-alcoholic steatohepatitis (NASH), and atherosclerosis, as well as other related conditions.

Simtuzumab is a monoclonal antibody against lysyl oxidase-like protein 2 (LOXL2). Simtuzumab can be used to treat primary sclerosing cholangitis (PSC) and is not effective in patients with bridging fibrosis or compensatory cirrhosis caused by non-alcoholic steatohepatitis.

Teneligliptin (MP-513) is a potent prolylthiazolidine-based DPP-4 inhibitor that competitively inhibits human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC50 values of approximately 1 nM.

THR-β agonist 3 is a potent agonist of THR-β with demonstrated research potential for metabolic diseases, including obesity, hyperlipidemia, hypercholesterolemia, diabetes, steatosis, non-alcoholic steatohepatitis (NASH), and atherosclerosis.

AMPK activator 6 (Compound GC) activates the AMPK pathway and reduces lipid content in HepG2 and 3T3-L1 cells. It significantly suppresses increases in total cholesterol (TC), low-density lipoprotein-C (LDL-C), triglyceride (TG), and other biochemical indices in blood serum, holding research value in non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome.

NLRP3-IN-20 (compound 11) is an orally administered inhibitor targeting the NLRP3 inflammasome, exhibiting potent inhibition with an IC50 of 25 nM against IL-1β secretion. It possesses excellent pharmacokinetic properties and has shown significant efficacy in models of non-alcoholic steatohepatitis, fatal septic shock, and colitis [1].

Resolvin E2 (RvE2) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acidviaan 18-HEPE intermediate, which is formed by aspirin-acetylated COX-2-mediated oxidation of EPA, by 5-lipoxygenase (5-LO) in human polymorphonuclear (PMN) neutrophils.2,3RvE2 (20 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of peritonitis induced by zymosan A .3Hepatic RvE2 levels are increased in mice fed normal chow, as well as in a mouse model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), by dietary supplementation with EPA.4Plasma levels of RvE2 are increased by dietary supplementation with fish oil containing ω-3 polyunsaturated fatty acids (PUFAs) in patients with peripheral artery disease or chronic kidney disease.1,5,6 1.Chiang, N., and Serhan, C.N.Specialized pro-resolving mediator network: An update on production and actionsEssays Biochem.64(3)443-462(2020) 2.Tjonahen, E., Oh, S.F., Siegelman, J., et al.Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesisChemistry & Biology131193-1202(2006) 3.Sungwhan, F.O., Pillai, P.S., Recchiuti, A., et al.Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammationJ. Clin. Invest.121(2)569-581(2011) 4.Echeverría, F., Valenzuela, R., Espinosa, A., et al.Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: Involvement of resolvins RvE1/2 and RvD1/2J. Nutr. Biochem.6335-43(2019) 5.Ramirez, J.L., Gasper, W.J., Khetani, S.A., et al.Fish oil increases specialized pro-resolving lipid mediators in PAD (the OMEGA-PAD II trial)J. Surg. Res.238164-174(2019) 6.Barden, A.E., Shinde, S., Burke, V., et al.The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney diseaseProstaglandins Other Lipid Mediat.1361-8(2018)

Cisd2 agonist 1 is a potent CDGSH iron-sulfur structural domain 2 (CISD2) agonist (EC50: 34 nM) with potential anticancer activity for the study of non-alcoholic fatty liver disease (NAFLD).

THR-β agonist 2 is a potent agonist of THR-β with potential for studies of metabolic diseases (e.g., obesity, hyperlipidaemia, hypercholesterolaemia, diabetes, steatosis, non-alcoholic steatohepatitis [NASH], atherosclerosis, and other related conditions).