steatohepatitis

APD668 is a potent GPR119 agonist with EC50 of 2.7 nM and 33 nM for hGPR119 and ratGPR119, respectively.

Denifanstat (FASN-IN-2) is a fatty acid synthase (FASN) inhibitor (IC50=0.052 μM, EC50=0.072 μM) with selective and oral activity. Denifanstat has been used in studies of steatohepatitis.

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

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.

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.

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

Efinopegdutide (JNJ-64565111) is a potent dual agonist for the glucagon-like peptide-1 (GLP-1) and glucagon receptors (GluR), demonstrating efficacy in activating both receptors, with potential applications in the research of nonalcoholic steatohepatitis (NASH) [1].

HSD17B13-IN-28 (compound 47) is a potent inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), with an IC50 of < 0.1 μM using estradiol as a substrate. HSD17B13-IN-28 plays an important role in nonalcoholic fatty liver diseases (NAFLDs), including NASH (nonalcoholic steatohepatitis) [1].

HSD17B13-IN-17 (compound 9) serves as a potent inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13). It demonstrates inhibitory efficacy with IC50 values of ＜0.1 μM for estradiol and ＜1 μM for Leukotriene B3 as substrates. This compound is significant in the management of nonalcoholic fatty liver diseases (NAFLDs), including nonalcoholic steatohepatitis (NASH) [1].

HSD17B13-IN-19 (compound 16) acts as a potent inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), exhibiting IC50 values under 0.1 μM and under 1 μM when using estradiol and Leukotriene B3 as substrates, respectively. This compound is crucial in the treatment of nonalcoholic fatty liver diseases (NAFLDs), such as nonalcoholic steatohepatitis (NASH) [1].

HSD17B13-IN-40 (compound 6) serves as a potent inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), exhibiting an IC50 value of less than 0.1 μM using estradiol as substrates. This compound is significant in the treatment of nonalcoholic fatty liver diseases (NAFLDs), including nonalcoholic steatohepatitis (NASH) [1].

HSD17B13-IN-42 (compound 10) is a potent inhibitor of hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), with an IC50 of < 0.1 μM using estradiol as substrates. HSD17B13-IN-42 plays an important role in nonalcoholic fatty liver diseases (NAFLDs) including NASH (nonalcoholic steatohepatitis) [1].

HSD17B13-IN-30 (compound 64) serves as a potent inhibitor of hydroxysteroid 17?-dehydrogenase 13 (HSD17B13), exhibiting an IC 50 value of less than 0.1 μM? with estradiol? as substrates. This compound is significantly implicated in the management of nonalcoholic fatty liver diseases (NAFLDs), including nonalcoholic steatohepatitis (NASH) [1].

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)

ZLY28 is a novel, first-in-class compound with specific intestinal restriction and oral activity, serving as a dual modulator of FXR and FABP1. Additionally, it is a pioneering anti-NASH agent, utilized in the study of nonalcoholic steatohepatitis (NASH) [1].

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).

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.

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.

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.

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].

CTPI-2 is an inhibitor of mitochondrial citrate carrier SLC25A1 with(KD : 3.5 μM). CTPI-2 inhibits glycolysis, PPARγ, and its downstream target the glucose transporter GLUT4. CTPI-2 exhibits anti-tumor activity.CTPI-2 halts salient alterations of NASH reverting steatosis, preventing the evolution to steatohepatitis, reducing inflammatory macrophage infiltration in the liver and adipose tissue, and starkly mitigating obesity induced by a high-fat diet.

11,12-DiHETrE, a Cytochrome P450 (P450) eicosanoid and endogenous metabolite, holds potential as a single biomarker for differentiating nonalcoholic fatty liver (NAFL) from nonalcoholic steatohepatitis (NASH) [1] [2]. Additionally, it is utilized in preterm labor research.

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)

V023-9340 is a powerful FXR inhibitor with an IC50 of 4.27 μM, suitable for research in NASH (nonalcoholic steatohepatitis) [1].