non-alcoholic fatty liver disease (nafld)

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

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.

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.

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)

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)

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.

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.

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) .

Fazpilodemab (BFKB8488A) is a fully humanized bispecific antibody selectively targeting and activating the Klotho β and fibroblast growth factor receptor 1c receptor complex, which can be used to study non-alcoholic fatty liver disease (NAFLD).

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).

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-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].

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].

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).

HSD17B13-IN-11 (Compound 2), with IC50 values of ≤ 1 μM for leukotriene B3 and ≤ 0.1 μM for estradiol, effectively inhibits hydroxysteroid 17β-dehydrogenase 13 (HSD17B13). This compound is utilized in studying various medical conditions including liver diseases, metabolic and cardiovascular disorders, particularly non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and drug-induced liver injury (DILI) [1].

HSD17B13-IN-59 (Compound 177), a potent inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), exhibits an IC 50 value of ≤ 0.1 μM for estradiol. This compound is applicable in research related to liver, metabolic, and cardiovascular diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and drug-induced liver injury (DILI) [1].

HSD17B13-IN-66 (Compound 146), an inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), shows a potent IC 50 value of ≤ 0.1 μM for estradiol. This compound is primarily utilized in research pertaining to liver diseases, metabolic disorders, and cardiovascular conditions, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and drug-induced liver injury (DILI) [1].

HSD17B13-IN-79 (Compound 32), an inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), demonstrates potent activity with an IC50 value of ≤ 0.1 μM against estradiol. This compound is primarily utilized in the study of liver, metabolic, and cardiovascular diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and drug-induced liver injury (DILI) [1].

HSD17B13-IN-81 (Compound 154) serves as an inhibitor targeting hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), exhibiting potent activity with an IC 50 of ≤ 0.1 μM against estradiol. This compound is applicable in the study of various health conditions, including liver, metabolic, and cardiovascular diseases, particularly non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and drug-induced liver injury (DILI) [1].

PXL770, a direct AMP kinase activator, is utilized in researching non-alcoholic fatty liver disease (NAFLD) [1].

YGT-31 is a PPARγ modulator with an IC50 of 1.72 μM and a Ki of 0.62 μM. It diminishes blood glucose levels and enhances insulin sensitivity in a type 2 diabetes model in db db mice by inhibiting CDK5-mediated phosphorylation of PPARγ-Ser273. Additionally, YGT-31 exhibits anti-steatotic effects in a mouse model of non-alcoholic fatty liver disease (NAFLD).

HSD17B13-IN-103 (Compound 44) serves as an inhibitor of HSD17B13. It is utilized in research related to non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

GprA, a novel synthetic agonist for G Protein-Coupled Receptor 120 Free Fatty Acid Receptor 4 (GPR120 FFAR4), demonstrates an AC50 of 203 nM on the full-length human GPR120 isoform. It is valuable for research into non-alcoholic fatty liver disease (NAFLD).