steatosis

Orotic acid (Vitamin B13) is an intermediate product in pyrimidine metabolism.

Orotic acid zinc (Zinc Orotate) salt dihydrate is an intermediate product in pyrimidine synthesis.

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

Scopolin (Scopoloside) formation is increased by the enhanced activity of PAL. Scopolin can reduce the clinical symptoms of rat AIA by inhibiting inflammation and angiogenesis, and this compound may be a potent agent for angiogenesis related diseases and can serve as a structural base for screening more potent synthetic analogs.

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.

ACH-000143 have been identified as a novel agonist of the melatonin receptors MT1 and MT2.

4-Hydroxyflavanone is a natural product, shows full vasorelaxing effects

LI-2242 is a potent inositol hexakisphosphate kinase (IP6K) inhibitor with IC50s of 31 nM, 42 nM, 8.7 nM, and 1944 nM for IP6K1, IP6K2, IP6K3, and IPMK, respectively.LI-2242 ameliorated hepatic steatosis by reducing the expression of genes that enhance lipid uptake, lipid stabilization, and adipogenesis, and enhanced mitochondrial oxygen consumption rate (OCR) and insulin signaling in adipocytes and hepatocytes in vitro. LI-2242 ameliorated diet-induced obesity, hyperglycemia and hepatic steatosis in mice.LI-2242 can be used to study type II diabetes, obesity, metabolic complications, venous thrombosis and psychiatric disorders.

Obeticholic Acid (6-ECDCA, INT-747) is a high-affinity, semisynthetic, bile acid-derived FXR agonist with an EC50 of 99 nM and is able to upregulate IκB-α, KLF-2, and KLF-4 expression. Obeticholic Acid (6-ECDCA, INT-747) also shows potential for treating hepatic steatosis, inflammation, and fibrosis while increasing insulin sensitivity.

MK-0626 is an orally available dipeptidyl peptidase IV (DPP-4) inhibitor that attenuates hepatic steatosis and accumulation by enhancing AMPK activity.MK-0626 attenuates TAC-induced diabetic pancreatic islet injury by restoring the expression of GLP-1R.MK-0626 is able to increase circulating endothelial progenitor cell numbers and endothelial-type nitric oxide synthase expression by promoting neoangiogenesis.

LP-533401 hydrochloride is a peripheral Tph inhibitor that cannot cross the blood-brain barrier that inhibits 5-hydroxytryptamine synthesis and can be used to study periodontal disease and hepatic steatosis.

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.

Anti-NASH agent 2 (compound 21) is an inhibitor of neolipogenesis activity and α-SMA gene expression. It improves hepatic steatosis, edema, inflammatory infiltration, and liver fibrosis in NASH mouse models.

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).

PPARα agonist5 is an orally active, selective partial agonist of PPARα with an EC50 of 3 nM. It reduces lipid accumulation and upregulates PPARα target genes, exhibiting anti-hepatic steatosis properties. Additionally, PPARα agonist5 demonstrates significant lipid-lowering and glucose-lowering effects through partial PPARγ agonist activity and mild inhibition of protein tyrosine phosphatase 1B (PTP1B) with an IC50 of 79.1 μM. It has favorable safety and is applicable in the study of dyslipidemia in type 2 diabetes.

THR-β agonist 2 diacetate (Compound 3) is a potent THR-β agonist with potential applications in researching metabolic disorders such as obesity, hyperlipidemia, hypercholesterolemia, and diabetes, as well as other conditions like steatosis and non-alcoholic steatohepatitis (NASH), atherosclerosis, and other related diseases and conditions.

ACC-IN-1 (Compound B1) is an allosteric inhibitor of acetyl-CoA carboxylase (ACC). It targets ACC to regulate lipid metabolism, potentially improving liver steatosis and inflammation associated with non-alcoholic steatohepatitis (NASH).

TBPH exacerbates liver steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) mouse models. It induces phospholipid metabolism disorders, reducing cardiolipin (CL) and phosphatidylserine (PS) levels. TBPH impairs endoplasmic reticulum-mitochondria (ER-Mito) contact, leading to mitochondrial dysfunction. Additionally, TBPH causes lung injury through mitochondrial-derived ds-DNA-mediated inflammatory responses. TBPH is utilized to study the role of MFN2-mediated ER-Mito contact in lipid metabolism homeostasis.

FASN/SCD-IN-1 is a Silybin derivative and an orally active inhibitor of fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD). In vitro, FASN/SCD-IN-1 demonstrates the ability to inhibit lipid deposition, reduce the transcription levels of FASN and SCD, and exhibits antioxidant, anti-inflammatory, and antifibrotic activities. It shows significant hepatoprotective effects in rat models of acute liver injury and improves pathological features such as steatosis, inflammation, and fibrosis in a mouse model of myeloproliferative-associated steatohepatitis (MASH). FASN/SCD-IN-1 can be used for MASH research.

5-Chloro-2-[[[2-[[3-(furan-2-yl)phenyl]amino]-2-oxoethoxy]acetyl]amino]benzoic acid is a novel orally active PAI-1 inhibitor that modulates fibrinolysis and metabolism-related pathways by downregulating PAI-1 activity, thereby improving metabolic parameters and alleviating hepatic steatosis in a high-fat diet mouse model.

THR-β agonist 11 is an orally active and selective thyroid hormone receptor (THR-β) agonist. It demonstrates robust cholesterol-lowering effects in cholesterol-fed rats. In a high-fat diet-carbon tetrachloride (HFD-CCl4) induced model of metabolic dysfunction-associated steatohepatitis (MASH) in mice, THR-β agonist 11 significantly reduces serum total triglycerides (TG), low-density lipoprotein cholesterol (LDL-cholesterol), liver total cholesterol (TC), and TG levels. Additionally, it alleviates hepatic steatosis, inflammation, and fibrosis. THR-β agonist 11 is applicable in the study of MASH and other fibrotic diseases.

THR-β agonist 10 is an orally active and selective THR-β agonist with an EC50 value of 11 nM. It effectively lowers levels of ALT (alanine aminotransferase), TC (total cholesterol), and LDL-C (low-density lipoprotein cholesterol). In mouse models of metabolic dysfunction-associated steatohepatitis (MASH), it improves steatosis, ballooning, inflammation, and fibrosis. THR-β agonist 10 is utilized in the research of MASH.

TBPH is a brominated flame retardant that exacerbates hepatic steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) mouse models. It disrupts phospholipid metabolism, reducing levels of cardiolipin (CL) and phosphatidylserine (PS). TBPH impairs endoplasmic reticulum-mitochondria (ER-Mito) contact, leading to mitochondrial dysfunction. Additionally, TBPH induces lung injury through a mitochondrial-derived ds-DNA mediated inflammatory response. It is also used to investigate the role of MFN2-mediated ER-Mito contact in lipid metabolism homeostasis.

FXR agonist15 is a selective, potent, orally active farnesoid X receptor (FXR) agonist with an EC50 of 0.76 μM. It does not significantly activate other nuclear receptors such as LXRα/β, PXR, PPARα/β/γ, and THR-β, with EC50 values exceeding 10 μM for each. FXR agonist15 is effective in alleviating symptoms like steatosis, lobular inflammation, hepatocellular ballooning, and liver fibrosis. It is applicable in research studies related to non-alcoholic steatohepatitis (NASH).