steatosis

SBI993 is an analog of SBI-477 and can be used as a biomarker to confirm the expected action of MondoA target gene expression in vivo. SBI993 reduces muscle TAG levels and hepatic steatosis.

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

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.

1. Eriocitrin (Eriodictyol-7-O-Rutinoside) is powerful antioxidative flavonoid; (1) Prevents oxidative damages caused by acute exercise-induced oxidative stress.(2) Lipid-lowering effects in a rat model of high-fat diet. 2. Dietary Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis. 3. Eriocitrin and Apigenin were identified as new potent inhibitors of human carbonic anhydrase VA isozyme.

L-Chicoric Acid (trans-Caffeoyltartaric acid) has been shown to inhibit hyaluronidase and HIV-1 integrase, and to possess phagoeytosis stimulatory activity in vitro and in vivo and antiviral acitivy. L-Chicoric acid may reduce acute alcohol-induced steatosis in mice through interfering with the induction of iNOS and iNOS-dependent signaling cascades in the liver. 3. L-Chicoric acid inhibited cell viability and induced apoptosis in 3T3-L1 preadipocytes which was characterized by chromatin condensation and poly ADP-ribose-polymerase (PARP) cleavage.

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.

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)

Tripalmitolein is a triacylglycerol that contains palmitoleic acid at the sn-1, sn-2, and sn-3 positions. It reduces red blood cell deformability in a concentration-dependent manner in a Reid's filtration assay. Hepatic levels of 1,2,3-tripalmitoleoyl-rac-glycerol are increased in the JAK2L mouse model of hepatic steatosis. Tripalmitolein plasma levels are decreased in renal patients before dialysis.

1-Pentadecanoyl-rac-glycerol is a monoacylglycerol that contains pentadecanoic acid at the sn-1 position. It has been found in wheat bran extracts.1 1-Pentadecanoyl-rac-glycerol levels are increased in a HepaRG cell-based model of hepatic steatosis induced by BSA-conjugated palmitate.2 |1. Prinsen, P., Gutiérrez, A., Faulds, C.B., et al. Comprehensive study of valuable lipophilic phytochemicals in wheat bran. J. Agric. Food Chem. 62(7), 1664-1673 (2014).|2. Brown, M.V., Compton, S.A., Milburn, M.V., et al. Metabolomic signatures in lipid-loaded HepaRGs reveal pathways involved in steatotic progression. Obesity (Silver Spring) 21(12), E561-E570 (2013).

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

Ethoxyquin dimer is an antioxidant and metabolite of ethoxyquin .1 It prevents oxidation of polyunsaturated fatty acids in fish meal and fish oil. Dietary administration of ethoxyquin dimer (0.1, 0.3, and 0.5% w/w) induces microvesicular steatosis and hepatocyte necrosis, as well as increases liver levels of oxidized glutathione and total lipids in mice.2

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

Calcium palmitate, a long-chain saturated fatty acid prevalent in animals and plants, induces the expression of glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in mouse granulosa cells. It is employed to establish a cell steatosis model [1] [2].

SRI-37330 inhibits glucagon secretion and function, reduces hepatic glucose production, and reverses hepatic steatosis.

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)

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).

1. Rhapontin (Ponticin) can alleviate liver steatosis and improve blood glucose and lipid profiles in KK/Ay diabetic mice, indicates that rhaponticin has a noticeable antidiabetic effect and could be potentially used as a new agent to treat type 2 diabetes mellitus and its complications.

Mannan is isolated from algae, mushrooms, yeast and higher plants and acts as an immunomodulator.Mannan inhibits the pro-inflammatory activity of hepatic macrophages (M1 lineage) with protective effects against many liver lesions such as necrosis or steatosis.

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.

O-1602 is a novel GPR55 agonist, an atypical cannabinoid associated with the central nervous system and obesity, and is a candidate compound for the treatment of cystitis.O-1602 promotes hepatic steatosis through GPR55 and PI3 kinase / Akt / SREBP-1c signalling in mice.O-1602 induces, in a GPR3-independent manner, in Hep55B cells with elevated intracellular calcium.

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)

Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses[3]. In C3-/- mice alcohol-induced liver steatosis is absent or strongly reduced after chronic or acute alcohol exposure. This suggests that the complement system and its component C3 contribute to the development of alcohol-induced fatty liver and its consequences[4].AMY-101 TFA (Cp40 TFA) is a peptidic inhibitor of the central complement component C3 (KD: 0.5 nM). It shows a favorable anti-inflammatory activity in models with COVID-19 severe pneumonia with systemic hyper inflammation[5].a daily subcutaneous dose of AMY-101 (4 mg/kg bodyweight) was protective against NHP periodontitis, suggesting that patients treated for systemic disorders (e.g., paroxysmal nocturnal hemoglobinuria) can additionally benefit in terms of improved periodontal condition[6].Plasma concentrations of both C3 and Cp40 were measured periodically and complete saturation of plasma C3 was confirmed. No differences in hematological, biochemical, or immunological parameters were identified in the blood or tissues of animals treated with Cp40 when compared to those injected with vehicle alone. Further, skin wounds showed no signs of infection in those treated with Cp40.Cp40 treatment was associated with a trend toward accelerated wound healing when compared with the control group. In addition, a biodistribution study in a rhesus monkey indicated that the distribution of Cp40 in the body is associated with the presence of C3, concentrating in organs that accumulate blood and produce C3[7].

Hexacosanol activates AMPK and hepatic autophagy and inhibits SREBP2, resulting in hypocholesterolemic activities and improvement of hepatic steatosis.

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) .

C22 Sphingomyelin is a naturally occurring form of sphingomyelin . Plasma levels of C22 sphingomyelin positively correlate with hepatic steatosis severity in patients with chronic hepatitis C virus (HCV). C22 Sphingomyelin levels are decreased in T-47D mammary epithelial cells and increased in MDA-MB-231 breast cancer cells relative to C16 sphingomyelin .

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

THR-β agonist 3 is a potent agonist of THR-β. THR-β agonist 3 has shown research potential for metabolic diseases such as obesity, hyperlipidemia, hypercholesterolemia, diabetes and other conditions such as steatosis and non-alcoholic steatohepatitis (NASH), atherosclerosis and other related conditions and diseases.

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.

FXR agonist 3, an anti-NASH (Non-Alcoholic Steatohepatitis) agent, functions by activating FXR. It demonstrates anti-fibrogenic activity by inhibiting the expression of COL1A1, TGF-β1, α-SMA, and TIMP1. Additionally, it significantly mitigates liver steatosis and inflammation and enhances the liver fibrosis level [1].

MHY 553 is a PPARα agonist that improved aged-induced hepatic steatosis.

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

p-nitro-Pifithrin-α is a cell-permeable analog of pifithrin-α, a potent p53 inhibitor. It suppresses p53-mediated TGF-β1 expression in HK-2 cells and inhibits the activation of caspase-3 by Zika virus (ZIKV) strains. Moreover, p-nitro-Pifithrin-α attenuates steatosis and liver injury in mice subjected to a high-fat diet, mitigating the effects of non-alcoholic fatty liver disease [1] [2] [3] [4].

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

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