GLP-1R modulator-3
GLP-1R modulator-3 is an orally active positive allosteric modulator of GLP-1R, with a Kd of 11.4 μM. GLP-1R modulator-3 exhibits no intrinsic GLP-1R agonistic activity. GLP-1R modulator-3 exerts a hypoglycemic effect in hGLP-1R knock-in mice. GLP-1R modulator-3 is applicable for the research of type 2 diabetes .
For research use only. We do not sell to patients.
- Formula: C21H26F3N3O
- Molecular Weight:393.45
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
GLP-1 11.4 μM (Kd) |
In Vitro
GLP-1R modulator-3 (Compound 5b) (10 μM) exhibits superior GLP-1R positive allosteric potentiating activity, producing 44.8% potentiation of the GLP-1 Emax at 10 μM in hGLP-1R HEK-293 T cells[1].
GLP-1R modulator-3 (0-10 μM; 15 min) acts as a characteristic positive allosteric modulator that concentration-dependently potentiates cAMP accumulation stimulated by both full-length GLP-1(7-36) and its metabolite GLP-1(9-36), with no intrinsic agonist activity in the absence of orthosteric peptide ligand in hGLP-1R HEK293T cells[1].
GLP-1R modulator-3 (3.12-50 μM) exhibits direct, measurable binding affinity for purified GLP-1R protein, with a Kd value of 11.4 μM[1].
GLP-1R modulator-3 (6.25-200 μM; 24 h) has lower cytotoxicity than the lead compound V-0219 (HY-143312) at concentrations of 50, 100, and 200 μM in HEK-293 T cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK-293 T cells
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Concentration:6.25, 50, 100, 200 μM
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Incubation Time:24 h
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Result:Exhibited significantly lower cytotoxicity than the lead compound V-0219 at the three higher tested concentrations (50 μM, 100 μM, 200 μM) across the 6.25 to 200 μM concentration range, indicating a more favorable safety profile across its active concentration range.
Parmacokinetics
| Species | Dose | Route | Tmax | Cmax | AUC0-t | AUC0-∞ | MRT0-∞ | T1/2 |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 30 mg/kg | p.o. | 1.33 h | 735 ng/mL | 12300 ng·h/mL | 25800 ng·h/mL | 38.3 h | 27.7 h |
In Vivo
GLP-1R modulator-3 (30 mg/kg; p.o.; single dose) exerts in vivo hypoglycemic effect in hGLP-1R KI mice that is fully mediated through the GLP-1 receptor[1].
GLP-1R modulator-3 (30 mg/kg; p.o.; single dose) provides superior in vivo glucose-lowering efficacy relative to the parent lead compound V-0219 in hGLP-1R KI mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6-Glp1rem2(hGLP−1R)Smoe human GLP-1R knock-in (12-week-old male)[1]
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Dosage:30 mg/kg; 60 mg/kg
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Administration:p.o.; single dose
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Result:Suppressed the post-challenge rise in blood glucose in a dose-dependent manner.
Reduced the 0-120 minute area under the blood glucose-time curve (AUC) compared to control, with the 60 mg/kg group demonstrating greater efficacy than the 30 mg/kg group.
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Animal Model:C57BL/6-Glp1rem2(hGLP−1R)Smoe human GLP-1R knock-in (12-week-old male)[1]
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Dosage:30 mg/kg
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Administration:p.o.; single dose
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Result:Had its blood glucose-lowering effect almost completely reversed by co-administration of the GLP-1R antagonist Exendin(9-39).
Produced a post-glucose 120-minute blood glucose AUC that was comparable to control group AUC and significantly higher than the AUC of the group receiving 30 mg/kg compound 5b alone.\nSignificantly blunted the post-glucose rise in blood glucose.
Produced a lower 120-minute post-glucose blood glucose AUC than the comparator compound V-0219 dosed at the same 30 mg/kg level.
Chemical Information
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Molecular Weight 393.45
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Formula C21H26F3N3O
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SMILES
FC(C1=CC=C(C2=NC(CN3CCC(CC3)N4CCCCC4)=CO2)C=C1)(F)F
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GLP-1R modulator-3 Related Classifications
HY-189219 Related Classifications
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