metabolic syndrome

Febuxostat (TEI 6720) is a xanthine oxidase inhibitor.

Lumiracoxib (Prexige) is a novel, selective COX-2 inhibitor with IC50 and Ki of 0.14 μM and 0.06 μM, exhibits 515-fold selectivity over COX-1. Phase 4.

K-111 (BM-170744) is an orally available peroxisome proliferator-activated receptor (PPAR)-alpha agonist and insulin enhancer for the study of obesity-type diabetes mellitus and the metabolic syndrome.

Granotapide is a microsomal triglyceride transfer protein (MTP) inhibitor that treats and rather prevents atherosclerosis, coronary artery disease, metabolic syndrome, obesity, diabetes mellitus, prediabetes mellitus, and hypertension.

GSK1940029 (SCD inhibitor 1) is an inhibitor of stearoyl-CoA desaturase (SCD).

HSD-016 is an orally active, selective and potent type 1 11β-hydroxysteroid dehydrogenase (11β-HSD1) inhibitor with strong inhibitory effects on human, mouse and rat 11β-HSD1.HSD-016 can be used in the study of diabetes and metabolic syndrome.

Apelin-13 is a 13-amino acid peptide sequence found in the central and peripheral nervous system that is an endogenous ligand for the G protein-coupled receptor angiotensin II protein J (APJ), with an EC50 value of 0.37 nM for APJ.Apelin-13 has vasodilatory and antihypertensive activity and can be used to study type 2 diabetic syndrome. Apelin-13 has vasodilatory and antihypertensive activities and can be used to study type 2 diabetes syndrome.

11β-HSD1-IN-12 is an 11β-HSD1 inhibitor.11β-HSD1-IN-12 is implicated in the conversion of glucocorticoids in vivo and can be used to study metabolic syndrome and obesity.

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

CB1 antagonist 1 is a CB1 receptor antagonist, used in the research of obesity and metabolic syndrome, neuroinflammatory disorders, cognitive disorders, and gastrointestinal disorders, psychosis, and cardiovascular.

Cevimeline hydrochloride hemihydrate ((-)-SNI-2011), a novel muscarinic receptor agonist, is being explored as a potential treatment for xerostomia in Sjogren's syndrome, exhibiting an IC50 value indicative of its affinity for mAChR. This compound's pharmacological effects on the gastrointestinal, urinary, and reproductive systems, alongside its impact on various tissues, were thoroughly examined in species including mice, rats, guinea pigs, rabbits, and dogs. The metabolic breakdown of (-)-SNI-2011 was studied in vitro using rat and dog liver microsomes to assess its biotransformation. Upon oral administration, peak plasma concentrations were reached within an hour in both rats and dogs, showcasing rapid absorption and a subsequent decrease in concentration with a half-life ranging from 0.4 to 1.1 hours. Bioavailability was noted at 50% in rats and 30% in dogs. Metabolic pathways highlighted significant species differences, with both S- and N-oxidized metabolites identified in rats, but only N-oxidized metabolites in dogs. Additionally, gender differences in pharmacokinetics were observed in rats but were absent in dogs. In vitro studies pinpointed the involvement of cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) in the metabolism of (-)-SNI-2011, specifically through sulfoxidation and N-oxidation processes, respectively. CYP2D and CYP3A were identified as the primary enzymes responsible for sulfoxidation in rat liver microsomes.

(+)-Cevimeline hydrochloride hemihydrate ((+)-SNI-2011), a potent muscarinic receptor agonist, shows promise as a therapeutic candidate for xerostomia in Sjogren's syndrome. It exhibits a broad pharmacological profile across various systems in animal models including mice, rats, guinea pigs, rabbits, and dogs. Metabolism studies using rat and dog liver microsomes reveal rapid absorption with peak plasma concentrations (Cmax) within one hour post-oral administration and a half-life (t1 2) between 0.4 to 1.1 hours. Bioavailability is 50% in rats and 30% in dogs. Metabolic analysis shows species-specific differences: rats produce S- and N-oxidized metabolites, while dogs produce only N-oxidized metabolites. Sex-based pharmacokinetic differences were noted in rats but not in dogs. In vitro studies indicate cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) involvement in the sulfoxidation and N-oxidation of SNI-2011, with CYP2D and CYP3A mainly responsible for sulfoxidation in rat liver microsomes.

AZ-Dyrk1B-33 (3-(2-Methyl-4-pyrimidinyl)-1-(phenylmethyl)-1H-pyrrolo[2,3-c]pyridine) is a potent and selective Dyrk1B kinase inhibitor with an IC50 of 7 nM.

FAPy-adenine HCl is a metabolic marker for Attention Deficit Hyperactivity Syndrome and is a mutagenic product of ROS-induced DNA damage.

LTD4 antagonist 2 (compound 6) functions as a leukotriene D4 (LTD4) antagonist with an IC50 of 2.8 μM for the cysteinyl leukotriene 1 receptor (CysLT1R). Additionally, it acts as an agonist for the G protein-coupled bile acid receptor 1 (GPBAR1), making it applicable for research into colitis, metabolic syndrome, and other GPBAR1- and CysLT1R-related diseases.

PPARγmodulator-3 (Compound 11) is a modulator of the peroxisome proliferator-activated receptor γ (PPARγ) with a KD value of 186 nM. It holds potential for research into insulin resistance (IR)-related conditions, including type 2 diabetes mellitus (T2DM) and metabolic syndrome.

Fluasterone, an NF-κB activation inhibitor, is used potentially for the treatment of metabolic syndrome.

K118 is an inhibitor of SH2-containing inositol 5' phosphatase 1 (SHIP1). It reverses diet- and age-associated obesity and metabolic syndrome.

SKI2852 is an orally active, selective, and efficient 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, improving metabolic syndrome in diabetic mouse models.

Voacamine (Voacanginine) is an indole alkaloid. Voacamine exhibits potent cannabinoid CB1 receptor antagonistic activity. Voacamine also inhibits P-glycoprotein (P-gp) action in multidrug-resistant tumor cells.Voacanginine may have rhythmic effects.

MK-0916 is a 11β-hydroxysteroid dehydrogenase type 1 inhibitor indicated for the treatment of type 2 diabetes and metabolic syndrome as well as obesity-related diseases.

Teduglutide (ALX-0600) is a glucagon-like peptide-2 analog that increases intestinal absorption by promoting mucosal growth and reducing mucosal degradation, improving intestinal recovery. It is used in the study of short bowel syndrome (SBS). Teduglutide activates NR4a1/nur77 expression and FXR signaling, alleviating intestinal dysfunction in mice and improving lung injury, making it useful for studying metabolic and cardiovascular diseases.

Palmitic acid-13C (C1, C2, C3, and C4 labeled) is intended for use as an internal standard for the quantification of palmitic acid by GC- or LC-MS. Palmitic acid is a common 16-carbon saturated fat that represents 10-20% of human dietary fat intake and comprises approximately 25 and 65% of human total plasma lipids and saturated fatty acids, respectively.1,2Acylation of palmitic acid to proteins facilitates anchoring of membrane-bound proteins to the lipid bilayer and trafficking of intracellular proteins, promotes protein-vesicle interactions, and regulates various G protein-coupled receptor functions.1Red blood cell palmitic acid levels are increased in patients with metabolic syndrome compared to patients without metabolic syndrome and are also increased in the plasma of patients with type 2 diabetes compared to individuals without diabetes.3,4 1.Fatima, S., Hu, X., Gong, R.-H., et al.Palmitic acid is an intracellular signaling molecule involved in disease developmentCell. Mol. Life Sci.76(13)2547-2557(2019) 2.Santos, M.J., López-Jurado, M., Llopis, J., et al.Influence of dietary supplementation with fish oil on plasma fatty acid composition in coronary heart disease patientsAnn. Nutr. Metab.39(1)52-62(1995) 3.Yi, L.-Z., He, J., Liang, Y.-Z., et al.Plasma fatty acid metabolic profiling and biomarkers of type 2 diabetes mellitus based on GC/MS and PLS-LDAFEBS Lett.580(30)6837-6845(2006) 4.Kabagambe, E.K., Tsai, M.Y., Hopkins, P.N., et al.Erythrocyte fatty acid composition and the metabolic syndrome: A National Heart, Lung, and Blood Institute GOLDN studyClin. Chem.54(1)154-162(2008)

L-hydroxy Arginine is a substrate for nitric oxide synthase in the catabolism of L-arginine to form nitric oxide. It has been used as a biomarker for reduced nitric oxide formation in patients with cardiovascular disease and metabolic syndrome.