dyslipidemia

MK-8245 analog is an analog of MK-8245 which is a liver-targeted Inhibitor of Stearoyl-CoA Desaturase (SCD). It is useful for the Treatment of Dyslipidemia and Diabetes.

GS-9667, a selective and partial agonist of the A(1) adenosine receptor (AR), represents an effective therapy for Type 2 diabetes (T2DM) and dyslipidemia via lowering of free fatty acids (FFA).

GW-493838 is a potent adenosine A1A receptor agonist for the treatment of dyslipidemia and neuropathic pain, with analgesic effects on post-herpetic neuralgia or peripheral nerve damage caused by trauma or surgery.

Muraglitazar (BMS-298585) is a PPAR α/γ dual agonist for the treatment of type 2 diabetes and associated dyslipidemia. Muraglitazar shows potent activity in vitro at human PPARα and PPARγ with EC50 of 320 nM and 110 nM respectively.

Phanginin A, a potent and orally active activator of salt-induced kinase 1 (SIK1), effectively inhibits gluconeogenesis, increases the expression of p-SIK1, and decreases the expression of p-CREB. By reducing blood glucose levels and enhancing glucose tolerance and dyslipidemia, Phanginin A holds potential for type 2 diabetes research.

Lycorine (Narcissine) inhibits protein synthesis and may inhibit ascorbic acid biosynthesis, although studies on the latter are controversial and inconclusive.

WAY-297848 is a novel glucokinase activator for the prevention or treatment of hyperglycemia, diabetes mellitus, obesity, dyslipidemia, and metabolic syndrome.

WAY-328127 is an active molecule, exhibiting an inhibitory effect on the (11β-hydroxysteroid dehydrogenase type 1) [(11β-HSD1)] enzyme. This modulation potentially leads to therapeutic applications in metabolic disorders, including (type 2 diabetes) [(T2D)] and metabolic syndrome. Its action in selectively downregulating (11β-HSD1) in adipose tissue suggests a favourable profile for addressing hyperglycemia and dyslipidemia.

Seladelpar (MBX 8025) has been used in trials studying the treatment of Hyperlipidemia.

Atorvastatin strontium is used primarily for lowering blood cholesterol and for prevention of events associated with cardiovascular disease. Like all statins, atorvastatin works by inhibiting HMG-CoA reductase, an enzyme found in liver tissue that plays a key role in production of cholesterol in the body.Atorvastatin is also used for the treatment of dyslipidemia.

KD-026 (SLx 4090), a microsomal triglyceride transfer protein (MTP) inhibitor(IC50 = 8.0 nM), is used in type 2 diabetes studies.

PPARα/γ agonist 1 is a potent and dual PPARα/γ partial agonist which is a promising prototype for the research of dyslipidemia and diabetes. PPARα/γ agonist 1 has EC50 values of 28 nM and 69 nM for PPARα and PPARγ, respectively [1].

GW590735 is an effective and selective PPARα agonist with an EC50 of 4 nM on PPARα and at least 500-fold selectivity versus PPARδ and PPARγ. GW590735 can be used in dyslipidemia studies.

MK 0767 is a dual peroxisome proliferator-activated receptor (PPAR) α/γ agonist that has been investigated as a potential treatment for type 2 diabetes and dyslipidemia.

Teneligliptin (MP-513) is a potent chemotype prolylthiazolidine-based DPP-4 inhibitor, which competitively inhibits human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC50s of approximately 1 nM. Teneligliptin (MP-513) inhibits all these DPP-4 enzymes in a concentration-dependent manner. The IC50s of Teneligliptin (MP-513) for rhDPP-4, human plasma, and rat plasma are 0.889, 1.75, and 1.35 nM, respectively. A study of enzyme inhibition kinetics is conducted for Teneligliptin (MP-513) using Gly-Pro-MCA as the substrate and rhDPP-4 as the enzyme source. Plots based on the Michaelis-Menten equation reveals that Teneligliptin (MP-513) inhibits DPP-4 in a substrate-competitivemanner; the residual sum of squares for competitive and non-competitive models is 0.162 and 0.192, respectively. Ki, Km, and Vmax values are 0.406 nM, 24 μM, and 6.06 nmol/min, respectively. Teneligliptin (MP-513) inhibits the degradation of GLP-1(7-36)amide with an IC50 of 2.92 nM[1]. Oral administration of Teneligliptin (MP-513) in Wistar rats results in the inhibition of plasma DPP-4 with an ED50 of 0.41 mg/kg. Plasma DPP-4 inhibition is sustained even at 24 h after administration of Teneligliptin (MP-513). An oral carbohydrate-loading test in Zucker fatty rats shows that Teneligliptin (MP-513) at ≥0.1 mg/kg increases the maximum increase in plasmaglucagon-like peptide-1 and insulin levels, and reduces glucose excursions. This effect is observed over 12 h after a dose of 1 mg/kg. An oral fat-loading test in Zucker fatty rats also shows that Teneligliptin (MP-513) at 1 mg/kg reduces triglyceride and free fatty acid excursions. In Zucker fatty rats, repeated administration of Teneligliptin (MP-513) for two weeks reduces glucose excursions in the oral carbohydrate-loading test and decreased the plasma levels of triglycerides and free fatty acids under non-fasting conditions. Oral administration of Teneligliptin (MP-513) inhibits plasma DPP-4 in rats in a dose-dependent manner. The ED50 value for Teneligliptin (MP-513) is calculated to be 0.41 mg/kg, while those for Sitagliptin and Vildagliptin, 27.3 and 12.8 mg/kg, respectively[1]. Teneligliptin (MP-513) improves the histopathological appearance of the liver and decreases intrahepatic triglyceride levels in an NAFLD model mouse, which is associated with downregulation of hepatic lipogenesis-related genes due to AMPK activation[2]. [1]. Fukuda-Tsuru S, et al. A novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, improves postprandial hyperglycemia and dyslipidemia after single and repeated administrations. Eur J Pharmacol. 2012 Dec 5;696(1-3):194-202. [2]. Ideta T, et al. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice. Int J Mol Sci. 2015 Dec 8;16(12):29207-18.

TRβ Agonist 1, a selective and mutation-sensitive thyroid hormone receptor β (TRβ) agonist, demonstrates an EC50 value of 21 nM. It is useful in the research of dyslipidemia, nonalcoholic steatohepatitis (NASH), and resistance to thyroid hormone (RTH) [1].

CP-868388 free base (CP-868388) is an orally active, potent and selective PPARα agonist with hypolipidemic and anti-inflammatory activity for the study of dyslipidemia.

DGAT1-IN-3 is a selective, potent, orally active DGAT-1 inhibitor that inhibits human DGAT-1 (IC50: 38 nM) and rat DGAT-1 (IC50: 120 nM).DGAT1-IN-3 can be used in studies of obesity, dyslipidemia and metabolic syndrome.

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.

Exicorilant is a selective and oral active glucocorticoid receptor (GR) antagonist (Ki: 7 nM) and it also has the potential to overcome adiposity, glucose intolerance, and dyslipidemia.

Atorvastatin magnesium trihydrate is used primarily for lowering blood cholesterol and for prevention of events associated with cardiovascular disease. Like all statins, atorvastatin works by inhibiting HMG-CoA reductase, an enzyme found in liver tissue that plays a key role in production of cholesterol in the body.Atorvastatin is also used for the treatment of dyslipidemia.

KRP297 is a PPAR agonist potentially for the treatment of type 2 diabetes and dyslipidemia.

PCSK9-IN-15 (compound 5) is a potent inhibitor of proprotein convertase subtilisin/kexin 9 (PCSK9, K D <200 nM) that plays a crucial role in cholesterol metabolism by regulating blood levels of low-density lipoprotein cholesterol (LDL-C). This compound is useful for researching cholesterol-lowering therapies and dyslipidemia [1].

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

SR9009 (Stenabolic), a REV-ERB agonist, increases the constitutive repression of genes regulated by REV-ERBα/ERBβ (IC50: 670/800 nM). Through activation of REV-ERB, SR9009 can decrease circadian locomotor activity during the dark phase and alter the expression pattern of core clock genes in the hypothalami of mice. The circadian pattern of expression of an array of metabolic genes in the liver, skeletal muscle, and adipose tissue was also altered in mice exposed to SR9009, resulting in increased energy expenditure. In Diet-induced obese mice, SR9009 (100 mg/kg, i.p., b.i.d., for 30 days) could decrease fat mass and markedly improve dyslipidemia and hyperglycemia.

SCD1 inhibitor-3 (ML-270) is a highly effective and orally available compound that inhibits SCD1 with remarkable safety. SCD1 inhibitor-3 demonstrates strong potential for research in metabolic diseases, including obesity, type II diabetes, and dyslipidemia, as well as various skin conditions like acne and cancer.

BCAT-IN-2 is an orally active and selective inhibitor of mitochondrial branched-chain aminotransferase (BCATm), inhibits BCATm and BCATc, and is used in obesity and dyslipidemia.

1. Fargesin ((+/-)-Fargesin) as a potential β1AR antagonist through cAMP/PKA pathway could protect against myocardial ischemia/reperfusion injury in rats. 2. Fargesin improves dyslipidemia and hyperglycemia by activating Akt and AMPK in WAT.