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.

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.

Azelaprag (AMG 986) is an oral apelin receptor agonist (EC50 = 0.32 nM). Azelaprag may be used to treat neurological disorders, cardiovascular diseases, and obesity with metabolic syndrome.

INT-777 (S-EMCA) is a potent, selective TGR5 agonist with an EC₅₀ of 0.82 μM. Following subarachnoid hemorrhage in rats, INT-777 inhibits NLRP5-ASC inflammasome-mediated neuroinflammation via the TGR3/cAMP/PKA signaling pathway. INT-777 exhibits multiple effects, including metabolic regulation, anti-inflammatory activity, cholagogue effects, and vascular protection. INT-777 can be used in research on diseases such as metabolic syndrome, non-alcoholic fatty liver disease, inflammatory bowel disease, and pulmonary arterial hypertension.

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.

Baicalin (Baicalein 7-O-β-D-glucuronide) is a prolyl endopeptidase inhibitor isolated from Scutellaria baicalensis that exhibits anti-inflammatory, antioxidant, antitumor, and antiviral activity. Baicalin can be used in research on inflammation, neurodegenerative diseases, tumors, and metabolic 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.

PPARα/γ agonist 3 (Compound 4) functions as a dual PPARα/γ agonist with anti-inflammatory properties. It significantly reduces inflammatory markers such as IL-6 and MCP-1 on THP-1 macrophages by inhibiting NF-κB activation. PPARα/γ agonist 3 is applicable for research on metabolic syndrome and metabolic dysfunction-associated fatty liver disease (MAFLD).

SLC3037 is an NLRP3 inhibitor that prevents the binding or oligomerization of NLRP3 with NEK7, thereby inhibiting inflammasome activation triggered by MSU and other activators. It is suitable for research related to gout, cardiovascular diseases, metabolic syndrome, or neurodegenerative diseases.

THR-β agonist 9 is a potent and selective THR-β activator, which shows sensitivity to His435 mutations with an EC50 of 3.2 nM. It demonstrates moderate selectivity, approximately 10-fold, and effectively activates various His435 mutants (H435A, H435Y, and H435R), with EC50 values ranging from 134.2 nM to 515.5 nM. THR-β agonist 9 presents potential for research into conditions such as dyslipidemia, metabolic syndrome-associated steatohepatitis (MASH), and resistance to thyroid hormone (RTH).

VU0514009 is a competitive antagonist of chemokine-like receptor 1 (CMKLR1) with an EC50 of 2 nM. It effectively inhibits chemerin-9-induced arrestin recruitment and receptor internalization, significantly reducing Ca2+ flux responses in HEK293 cells. This compound shows potential for research in inflammatory diseases and metabolic syndrome.

LaKe is an orally active simple ester prodrug. It shows potential for research in metabolic syndrome and neurodegenerative diseases.