LY3324954
Based on 1 Customer Validation
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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- Purity: 98.89%
- 화학식: C238H362N50O76
- 분자량:5139.71
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보관:
Sealed storage, away from moisture.
Powder -80°C, 2 years , -20°C, 1 year* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
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 | Tmax | Cmax | AUC0-inf | T1/2 | 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.; 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.
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Animal Model:C57Bl/6J (10-12-week-old male)[1]
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Dosage:10 nmol/kg
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Administration:s.c.; on day 1 and day 4
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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.
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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]
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Dosage:1-300 nmol/kg
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Administration:s.c.; every 72 hours; 14 days
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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
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Appearance Solid
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분자량 5139.71
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화학식 C238H362N50O76
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Color White to off-white
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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
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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
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Sequence Shortening
Y-Aib-QGTFTSDYSKYLD-Aib-KKA-Lys(AEEA-AEEA-γGlu-γGlu-C18 diacid)-EFVEWLLETGPSSGAPPPS-NH2
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Sealed storage, away from moisture
Powder -80°C 2 years -20°C 1 year * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
용액&용해도
In Vitro:
DMSO : 100 mg/mL (19.46 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (0.49 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (0.49 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
순도&문서
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Data Sheet (297 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[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]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.1946 mL | 0.9728 mL | 1.9456 mL | 4.8641 mL |
| 5 mM | 0.0389 mL | 0.1946 mL | 0.3891 mL | 0.9728 mL | |
| 10 mM | 0.0195 mL | 0.0973 mL | 0.1946 mL | 0.4864 mL | |
| 15 mM | 0.0130 mL | 0.0649 mL | 0.1297 mL | 0.3243 mL |
LY3324954 Related Classifications
HY-P11880 Related Classifications
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