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
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
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. Further protocols information, click here.
-
Cell Line:HEK-293 T cells
-
Concentration:6.25, 50, 100, 200 μM
-
Incubation Time:24 h
-
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.
-
Animal Model:C57BL/6-Glp1rem2(hGLP−1R)Smoe human GLP-1R knock-in (12-week-old male)[1]
-
Dosage:30 mg/kg; 60 mg/kg
-
Administration:p.o.; single dose
-
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.
-
Animal Model:C57BL/6-Glp1rem2(hGLP−1R)Smoe human GLP-1R knock-in (12-week-old male)[1]
-
Dosage:30 mg/kg
-
Administration:p.o.; single dose
-
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
-
Molecular Weight 393.45
-
Formula C21H26F3N3O
-
SMILES
FC(C1=CC=C(C2=NC(CN3CCC(CC3)N4CCCCC4)=CO2)C=C1)(F)F
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
-
Gene Editing
Gene editing modify specific sites within the genome through gene deletions, insertions or conversions to study functionally unknown genes or conduct gene therapy. It is also used to change the biological traits of organisms to establish new varieties. Gene editing techniques include zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas 9) (CRISPR/Cas9).
-
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
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GLP-1R modulator-3 Related Classifications
HY-189219 Related Classifications
Powered by Bioz