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Art. -Nr.: HY-P11880

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LY3324954

LY3324954 is a long-acting, highly selective glucagon receptor (GCGR) agonist. LY3324954 stimulates cAMP production via the hepatic GCGR signaling pathway and induces acute blood glucose elevation, while promoting FGF21 expression in the liver and plasma. LY3324954 reduces body weight and abdominal fat mass, increases energy expenditure, and effectively improves lipid homeostasis, insulin sensitivity, and glucose intolerance. LY3324954 can be used in obesity-related research.

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Formel: C₂₃₈H₃₆₂N₅₀O₇₆
Molecular Weight:5139.71

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

LY3324954 Chemical Structure

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

In Vitro

LY3324954 (1×10^-14 M - 1×10^-6 M; 30 min) potently activates human GCGR-expressing HEK293 cells with an EC₅₀ of 5.472×10^-10 M, demonstrating greater potency than native glucagon^[1].
LY3324954 stimulates glucose output from human iPSC-derived hepatocytes to a comparable extent as native glucagon^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Parmacokinetics

Species	Dose	Route	T_max	C_max	AUC_0-inf	T_1/2	CL/F
Mice^[1]	300 nmol/Kg	s.c.	6 h	668 nM	11899 nM·h	6.5 h	25 mL/h/kg
Rat^[1]	100 nmol/Kg	s.c.	8 h	425 nM	11692 nM·h	13 h	8.8 mL/h/kg
Dog^[1]	39 nmol/Kg	s.c.	14 h	303 nM	28077 nM·h/mL	49 h	1.4 mL/h/kg
Monkey^[1]	50 nmol/Kg	s.c.	9 h	425 nM	31821 nM·h/mL	44 h	1.6 mL/h/kg

In Vivo

LY3324954 (10 nmol/kg; s.c.; on day 1 and day 4) stimulates transient glucose excursions and progressive insulin secretion in lean C57Bl/6J mice, with enhanced glucose tolerance observed after 7 days of biweekly dosing^[1].
LY3324954 (10 nmol/kg; s.c.; single dose) stimulates acute blood glucose elevation via a mechanism dependent on hepatic glucagon receptor signaling in mice^[1].
LY3324954 (1-300 nmol/kg; s.c.; every 72 hours; 14 days) induces dose-dependent body weight and fat mass loss in diet-induced obese mice, with improvements in liver and lipid homeostasis observed across all tested doses^[1].
LY3324954 (24 nmol/kg; s.c.; every 72 hours; 15 days) induces body weight and fat mass loss in diet-induced obese mice via increased energy expenditure and enhanced lipid oxidation, without reducing total food intake^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57Bl/6J (10-12-week-old male)^[1]
Dosage:

10 nmol/kg
Administration:

s.c.; on day 1 and day 4
Result:

Increased blood glucose at 30 and 60 minutes post-injection on day 1, with glucose returning to baseline by 120 minutes; the area under the curve (AUC) for glucose was significantly higher than vehicle.
On day 4, caused glucose excursion peak at 30 minutes followed by reduced blood glucose at 180 minutes, and the glucose AUC was significantly lower than on day 1.
Stimulated a subtle insulin excursion on day 1, with a robustly increased insulin excursion and AUC on day 4 compared to vehicle.
Induced a trend toward reduced 5-hour fasting blood glucose on day 7, along with enhanced glucose tolerance and a significantly lower glucose AUC during the tolerance test compared to vehicle.

Animal Model:

C57Bl/6J (22-24-week-old; diet-induced obesity via high-fat diet for 12 weeks, switched to 39.7% HFD for 4-8 weeks prior to treatment)^[1]
Dosage:

1-300 nmol/kg
Administration:

s.c.; every 72 hours; 14 days
Result:

Induced dose-dependent body weight loss, with significant loss observed at doses ≥10 nmol/kg.
Reduced food intake at 100 and 300 nmol/kg doses, but not at lower doses.
Reduced fat mass and change in fat mass from day 0 to day 14 in a dose-dependent manner, with significant reductions at ≥10 nmol/kg.
Maintained absolute lean mass similar to vehicle across all doses, but caused significant lean mass loss from day 0 to day 14 at 100 and 300 nmol/kg.
Significantly elevated blood glucose at 30 and 100 nmol/kg.
Significantly reduced alanine aminotransferase (ALT) at all doses.
Significantly reduced plasma cholesterol at 30, 100, and 300 nmol/kg.
Significantly reduced liver triglycerides at ≥10 nmol/kg.

Chemical Information

Molecular Weight 5139.71
Formel C₂₃₈H₃₆₂N₅₀O₇₆
SMILES

O=C(NC(C)(C)C(N[C@@H](CCC(N)=O)C(NCC(N[C@@H]([C@H](O)C)C(N[C@@H](CC1=CC=CC=C1)C(N[C@@H]([C@H](O)C)C(N[C@@H](CO)C(N[C@@H](CC(O)=O)C(N[C@@H](CC2=CC=C(C=C2)O)C(N[C@@H](CO)C(N[C@@H](CCCCN)C(N[C@@H](CC3=CC=C(C=C3)O)C(N[C@@H](CC(C)C)C(N[C@@H](CC(O)=O)C(NC(C)(C)C(N[C@@H](CCCCN)C(N[C@@H](CCCCN)C(N[C@@H](C)C(N[C@@H](CCCCNC(COCCOCCNC(COCCOCCNC(CC[C@@H](C(O)=O)NC(CC[C@@H](C(O)=O)NC(CCCCCCCCCCCCCCCCC(O)=O)=O)=O)=O)=O)=O)C(N[C@@H](CCC(O)=O)C(N[C@@H](CC4=CC=CC=C4)C(N[C@@H](C(C)C)C(N[C@@H](CCC(O)=O)C(N[C@@H](CC5=CNC6=CC=CC=C56)C(N[C@@H](CC(C)C)C(N[C@@H](CC(C)C)C(N[C@@H](CCC(O)=O)C(N[C@@H]([C@H](O)C)C(NCC(N7[C@@H](CCC7)C(N[C@@H](CO)C(N[C@@H](CO)C(NCC(N[C@@H](C)C(N8[C@@H](CCC8)C(N9[C@@H](CCC9)C(N%10[C@@H](CCC%10)C(N[C@@H](CO)C(N)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)[C@H](CC%11=CC=C(C=C%11)O)N
Sequence

Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Aib-Lys-Lys-Ala-Lys(EEA-AEEA-γGlu-γGlu-C18 diacid)-Glu-Phe-Val-Glu-Trp-Leu-Leu-Glu-Thr-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2
Sequence Shortening

Y-Aib-QGTFTSDYDKYLD-Aib-KKA-Lys(AEEA-AEEA-γGlu-γGlu-C18 diacid)-EFVEWLLETGPSSGAPPPS-NH2
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Handling Instructions (2659 KB)

Verweise

[1]. Roell W, Coskun T, Kim T, et al.. Characterization of LY3324954 a long-acting glucagon-receptor agonist. Molecular metabolism. 2025 Jan;91:102073. [Content Brief]

[2]. Bailey CJ, Flatt PR, Conlon JM. Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities. Peptides. 2025 May;187:171380. [Content Brief]

[3]. Suga T, Tabei Y, Kikuchi O, et al.. Sodium-glucose cotransporter-specific substrate αMG stimulates endogenous glucagon secretion and ameliorates obesity-associated metabolic disorders in mice. Molecular metabolism. 2026 Mar;105:102324. [Content Brief]

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Keywords

100 mg

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