steatohepatitis

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

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

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.

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.

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.

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.

KHK-IN-5 (Compound 18), a KHK inhibitor, is employed in the study of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and type 2 diabetes (T2DM).

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.

SHS206 (compound 6n) is an orally active mitochondrial uncoupler that decreases triglyceride levels in the liver. Demonstrating in vivo efficacy in a GAN mouse model, SHS206 also exhibits inhibitory effects on metabolic dysfunction-associated steatohepatitis (MASH).

LZ-007 is an agonist of the Farnesoid X receptor (FXR), with an EC50 of 51 nM as determined by TR-FRET assay, and an EC50 of 76 nM in HepG2 cells. It exhibits favorable pharmacokinetic properties in SD rats and can improve metabolic dysfunction-associated steatohepatitis induced by high-fat diets and CCl4 in mice.

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).

FXR/HSD17B13 modulator 1 (compound 6) is an effective modulator of FXR/HSD17B13, playing a significant role in studies related to metabolic dysfunction-associated steatohepatitis (MASH).

SHO1122147 (Compound 7m) disrupts the mitochondrial electron transport chain, demonstrating mitochondrial uncoupling activity (EC50=3.6 μM). It increases the cellular oxygen consumption rate (OCR=69%) and enhances cellular respiration. Additionally, SHO1122147 is orally active and can be utilized in research related to obesity and metabolic dysfunction-associated steatohepatitis (MASH).

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

BE2647 is a selective inhibitor of the mitochondrial pyruvate carrier (MPC), with an EC50 of 70 nM. It exhibits good metabolic stability in mouse liver microsomes. BE2647 can be utilized in research related to metabolic diseases, metabolic-associated steatotic liver disease (MASLD), or metabolic-associated steatohepatitis (MASH).

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.

AZD2389 is an effective and orally active FAP inhibitor that improves histological fibrosis and increases intact α2-AP, suitable for studying metabolic dysfunction-associated steatohepatitis.

Hydroxy tipelukast (Compound MN-002), a metabolite of Compound MN-001, is an orally active phenoxyalkyl carboxylic acid. It inhibits hepatic steatosis, lobular inflammation, hepatocellular ballooning, and liver fibrosis, while also reducing hepatic hydroxyproline levels. Hydroxy tipelukast is a promising candidate for the study of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

DA-1241 is a GPR119 agonist. By activating GPR119, it downregulates NFκB signaling, thereby inhibiting macrophage differentiation. Whether used alone or in combination with DPP4 inhibitors, DA-1241 can alleviate liver inflammation and restore the expression of liver genes linked to inflammation. It is applicable in the research of metabolic dysfunction-associated steatohepatitis (MASH).