YH18968
YH18968 is an orally active GPR119 agonist with an EC50 of 2.8 nM for inducing cAMP accumulation. YH18968 activates GPR119, elevates intracellular cyclic adenosine monophosphate levels, stimulates glucagon-like peptide-1 secretion from intestinal L cells, and triggers glucose-dependent insulin secretion from pancreatic β cells. YH18968 improves glucose tolerance in normal mice and diet-induced obese mice. YH18968 can be used for the research of type 2 diabetes.
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- CAS. Nr.: 1632498-56-6
- Formel: C27H28FN9O3
- Molecular Weight:545.58
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
Beschreibung
In Vitro
YH18968 (0.03-1000 nM; 60 min) stimulates insulin secretion in HIT-T15 cells in a dose-dependent manner, with an EC50 of 3.5 nM[1].
YH18968 (0.03-1000 nM; 120 min) stimulates GLP-1 secretion from GLUTag cells in a dose-dependent manner, with an EC50 of 0.1 nM[1].
YH18968 (0.1-100 μM; 48 h) exhibits extremely low cytotoxicity in HIT-T15, GLUTag and HepG2 cells, with an LC50 greater than 100 μM in all three cell lines[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HIT-T15 hamster insulinoma cells
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Concentration:0.03, 0.1, 0.3, 1, 3, 10, 30, 100, 300, and 1,000 nM nM (15 mM glucose condition); 100 nM (0, 3, or 15 mM glucose conditions)
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Incubation Time:60 min
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Result:Elicited dose-dependent increases in insulin release with an EC50 of 3.5 nM.
Enhanced insulin release in a glucose-dependent manner at 100 nM, with a significant increase observed at 15 mM glucose (2.19-fold vs control) and no effect in the absence of glucose.
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Cell Line:GLUTag murine intestinal L cells
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Concentration:0.03, 0.1, 0.3, 1, 3, 10, 30, 100, 300, and 1,000 nM
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Incubation Time:120 min
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Result:Enhanced GLP-1 secretion in a dose-dependent manner with an EC50 of 0.1 nM.
Parmacokinetics
| Species | Dose | Route | AUClast | AUC0-inf | CL | Vss | MRT | Cmax | Tmax | T1/2 | F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 1375.1 ng·h/mL | 1619.9 ng·h/mL | 617.3 mL/h/kg | 2112.2 mL/kg | 3.4 h | / | / | / | / |
| Mice[1] | 1 mg/kg | p.o. | 549.7 ng·h/mL | 719.8 ng·h/mL | / | / | / | 168.6 ng/mL | 0.5 h | 3.1 h | 40.0 % |
| Mice[1] | 10 mg/kg | p.o. | 2471.7 ng·h/mL | 2958.2 ng·h/mL | / | / | / | 759.7 ng/mL | 0.5 h | 2.6 h | 18.0 % |
| Mice[1] | 100 mg/kg | p.o. | 6538.0 ng·h/mL | 15773.9 ng·h/mL | / | / | / | 1472.2 ng/mL | 0.5 h | 9.2 h | 4.8 % |
In Vivo
YH18968 (0.1-10 mg/kg; p.o.; single dose) significantly improves glucose tolerance in DIO mice, with its efficacy reaching saturation at 1 mg/kg[1].
YH18968 (1 mg/kg; p.o.; once daily; for 28 consecutive days) for 4 consecutive weeks sustains improved glucose tolerance in DIO mice without rapid desensitization, and produces a synergistic effect when combined with Linagliptin (HY-10284)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (8-week-old, male)[1]
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Dosage:0.1 mg/kg; 1 mg/kg; 10 mg/kg; 10 mg/kg + 1 mg/kg linagliptin
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Administration:p.o.; single dose
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Result:Significantly lowered the 2-hour area under the curve (AUC) for blood glucose in a dose-dependent manner compared to vehicle control.
Produced a significant additive glucose-lowering effect when co-administered with 1 mg/kg linagliptin.
Increased active plasma GLP-1 levels by 2.7-fold compared to vehicle control at 30 minutes post-administration at 10 mg/kg dose.
Co-administration with linagliptin significantly increased active GLP-1 levels compared to either agent alone.
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Animal Model:diet-induced obese (DIO) (17-week-old, male, Type 2 diabetes model)[1]
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Dosage:0.1 mg/kg; 1 mg/kg; 10 mg/kg
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Administration:p.o.; single dose
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Result:Significantly lowered the 2-hour AUC for blood glucose compared to vehicle control at 1 and 10 mg/kg doses, with a dose-dependent effect observed.
Produced similar levels of glucose lowering at 1 and 10 mg/kg doses, indicating a saturated effect.
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Animal Model:diet-induced obese (DIO) (17-week-old, male, Type 2 diabetes model)[1]
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Dosage:1 mg/kg; 1 mg/kg + 1 mg/kg linagliptin
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Administration:p.o.; once daily; 28 days
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Result:Significantly lowered the 2-hour AUC for blood glucose compared to vehicle control on day 1, with a more potent effect than 10 mg/kg MBX2982 (HY-15291).
Produced an additive glucose-lowering effect when co-administered with 1 mg/kg linagliptin compared to either agent alone on day 1.
Continued to effectively lower the 2-hour AUC for blood glucose on day 29, maintaining glucose tolerance improvement equivalent to day 1 efficacy when used alone or in combination with Linagliptin.
Chemical Information
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CAS. Nr. 1632498-56-6
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Molecular Weight 545.58
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Formel C27H28FN9O3
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SMILES
O=C1N(C=NN1[C@H]2CCOC2)C3=C(F)C=C(C=C3)C=4C=C(C#N)C(=NC4)N5CCN(CC5)C=6N=C(C(C)C)ON6
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Protokoll
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Research Protocol for Endocrine Diseases
Endocrine diseases often arise from disrupted hormone production, hormone signaling, or target-tissue responsiveness; for diabetes-focused endocrine disease models, insulin signaling regulates glucose uptake, hepatic glucose output, lipid metabolism, and β-cell compensation. Type 2 diabetes develops through interacting defects in insulin resistance, β-cell dysfunction, adipose inflammation, hepatic glucose overproduction, altered incretin signaling, and ectopic lipid metabolism. A major unresolved question is whether endocrine dysfunction is driven primarily by target-tissue insulin resistance, intrinsic β-cell failure, immune/inflammatory stress, or combined multi-organ failure that differs by disease stage.
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Human Islet Cell Culture
The method of preserving islets in vitro, with purified reduced immunogenicity. The steps are islet isolation, islet cell purification, in vitro determination of islet function and islet cell culture.
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
Reinheit & Dokumentation
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Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
YH18968 Related Classifications
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