Cat. No.: HY-P11274

Zenagamtide

Name: Zenagamtide
Brand: MedChemExpress
SKU: HY-P11274
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(Synonyms: Amycretin; NN 9487)

Zenagamtide (Amycretin; NN 9487) sodium is an orally active, blood-brain barrier permeable triple agonist that targets GLP-1, Amylin Receptor and Calcitonin Receptor. Zenagamtide sodium is a single peptide consisting of 68 amino acids that can target brain regions regulating food intake, significantly suppress appetite and reduce energy intake. Therefore, Zenagamtide sodium improves body weight, waist circumference, glycated hemoglobin and lipid profile, and also alleviates the histological features of metabolic dysfunction-associated steatotic liver disease (MASLD) and enhances insulin sensitivity. Zenagamtide sodium may cause transient increases in heart rate and fluctuations in serum calcium levels, but it is an important compound for the study of overweight, obesity, insulin resistance and related metabolic diseases.

For research use only. We do not sell to patients.

CAS No.: 3005889-81-3
Formula: C₃₄₃H₅₅₀N₉₄O₁₁₆
Molecular Weight:7846.60

Storage:

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

Zenagamtide Chemical Structure

CAS No.: 3005889-81-3

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Use of MCE Products

Fluorescent Dye

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

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[1]

GLP-1

In Vitro

Zenagamtide (Amycretin; NN 9487) activates GLP-1, amylin, and calcitonin receptors in human, mouse, and rat cell systems^[1].
Zenagamtide (30 min-3 h) potently activates human, mouse, and rat GLP-1R, mouse and rat AMY_{3 (a)}R, and mouse and rat CTR, with EC₅₀ values ranging from 8.4×10^-13 M to 7.8×10^-11 M^[2].
Zenagamtide (30 min) potently activates human AMY_{1 (a)}R, AMY_{2 (a)}R, AMY_{3 (a)}R and CTR_(a), with EC₅₀ values ranging from 1.30×10^-12M to 1.72×10^-11M^[2].

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

In Vivo

Zenagamtide (Amycretin; NN 9487) reduces total energy intake and body weight and improves insulin sensitivity and metabolic health indicators in diet-induced obese rats after subcutaneous administration^[1].
Zenagamtide (10 nmol/kg; s.c.; single administration) reduces 48-hour cumulative food intake by 50% in normal-weight male Sprague Dawley rats^[2].
Zenagamtide (2-10 nmol/kg; s.c.; twice daily; for 21 consecutive days) reduces total food intake by 23-30% and induces vehicle-corrected body weight loss of 15.8-21.3% in a dose-dependent manner in male DIO C57Bl/6J mice^[2].
Zenagamtide (1-10 nmol/kg; s.c.; once daily; for 21 days) reduces total energy intake by 47.4% and achieves a vehicle-corrected 18.3% body weight loss in male diet-induced obese (DIO) Sprague Dawley rats while maintaining total energy expenditure^[2].
Zenagamtide (1-10 nmol/kg; s.c.; once daily; for 35 days) reduces HOMA-IR by 47% and increases the steady-state glucose infusion rate 3-fold in male diet-induced obese (DIO) Sprague Dawley rats, suggesting improved insulin sensitivity^[2].
Zenagamtide (10-30 nmol/kg; s.c.; twice daily; for 12 weeks) reduces plasma liver enzyme levels, improves the MASLD activity score in 55.6%-64.7% of mice, and decreases liver inflammation and fibrosis markers in biopsy-confirmed GAN DIO-MASH male C57BL/6JRj mice^[2].

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

Animal Model:

C57Bl/6J (male, 25 weeks old, 39-56 g, diet-induced obese)^[2]
Dosage:

2 nmol/kg; 10 nmol/kg
Administration:

s.c.; twice daily; 21 days
Result:

Reduced total 21-day food intake by 23% with 2 nmol/kg and 30% with 10 nmol/kg.
Induced vehicle-adjusted body weight loss of 15.8% with 2 nmol/kg and 21.3% with 10 nmol/kg, with a significant difference between the two target reagent doses.

Animal Model:

Sprague Dawley (male, ~750 g, diet-induced obese)^[2]
Dosage:

1 nmol/kg (day 1); 3 nmol/kg (day 2); 10 nmol/kg (days 3-21)
Administration:

s.c.; once daily; 21 days
Result:

Induced 18.3% vehicle-adjusted body weight loss after 21 days.
Reduced total energy intake by 47.4% compared to vehicle control.
Showed no significant difference in total energy expenditure compared to vehicle groups, while the calorie-restricted weight-matched group had 13.6% lower total energy expenditure than the target reagent group.

Animal Model:

Sprague Dawley (male, diet-induced obese)^[2]
Dosage:

1 nmol/kg (day 1); 3 nmol/kg (day 2); 10 nmol/kg (days 3-35)
Administration:

s.c.; once daily; 35 days
Result:

Reduced baseline fasting blood glucose by 7% (vehicle: 121.1 ± 3.0 mg/dL vs.
target reagent: 112 ± 2.1 mg/dL; p < 0.05).
Reduced baseline fasting plasma insulin by 42% (vehicle: 77.0 ± 6.7 µU/mL vs.
target reagent: 44.8 ± 4.0 µU/mL; p < 0.001).
Reduced HOMA-IR by 47% (vehicle: 23.4 ± 2.3 vs.
target reagent: 12.5 ± 1.2; p < 0.001).
Required a three-fold higher glucose infusion rate to maintain euglycaemia during clamp (average steady-state GIR: vehicle: 5.53 ± 1.17 mg/kg/min vs.
target reagent: 16.4 ± 2.10 mg/kg/min; p < 0.001).
Increased tracer-determined glucose uptake by 37% compared to vehicle control (vehicle: 15.7 ± 1.51 mg/kg/min vs.
target reagent: 24.8 ± 1.33 mg/kg/min; p < 0.001), while hepatic glucose production did not differ between groups.

Animal Model:

C57BL/6JRj (male, Gubra-Amylin NASH diet-induced obese metabolic dysfunction-associated steatotic liver disease, fibrosis stage F2-3, steatosis score 3, inflammation score ≥2)^[2]
Dosage:

10 nmol/kg (titrated: 0.5→1→2→6→10 nmol/kg); 30 nmol/kg (titrated: 0.5→1→2→6→12→30 nmol/kg)
Administration:

s.c.; twice daily; 12 weeks
Result:

Significantly reduced plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels with both doses (p < 0.001 vs.
vehicle).
Achieved ≥2-point improvement in MASLD activity score in 55.6% of mice treated with 10 nmol/kg and 64.7% treated with 30 nmol/kg (p < 0.001 vs.
vehicle, which had 0% improvement).
Significantly reduced liver galectin-3 staining (inflammation marker) with both doses (p < 0.05 for 10 nmol/kg, p < 0.01 for 30 nmol/kg vs.
vehicle).
Significantly reduced liver α-smooth muscle actin staining (fibrosis marker) with both doses (p < 0.001 vs.
vehicle).
Reduced hepatocytes with lipid droplets to 42.2% with 10 nmol/kg and 29.4% with 30 nmol/kg (p < 0.001 vs.
vehicle's 77.9%).

Animal Model:

C57BL/6J (male, 25 g)^[2]
Dosage:

100 nmol/kg
Administration:

i.v.; single dose
Result:

Detected fluorescent signal in circumventricular organs (area postrema, median eminence, vascular organ of the lamina terminalis, subfornical organ) and blood-brain barrier-protected regions (arcuate hypothalamic nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve) at 2 and 6 hours post-dose.
Showed highest signal intensity in circumventricular organs at 2 hours post-dose.

Related Protocols :

Chemical Information

CAS No. 3005889-81-3
Molecular Weight 7846.60
Formula C₃₄₃H₅₅₀N₉₄O₁₁₆
Synonyms

Amycretin; NN 9487
Sequence

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

H-Aib-EGTFTSDVSSYLEEQAAREFIAWLVRGR-{Lys(AEEA-AEEA-γGlu-C18 diacid)}-GGGGEASELSTAALGRLSAELHELATLPRTETGSGSP-NH2
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

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

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (340 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study[J]. The Lancet, 2025, 406(10499): 149-162.

[2]. Kuhre RE, et al. The effect of amycretin, a unimolecular glucagon-like peptide-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats. EBioMedicine. 2025;118:105862. [Content Brief]

[3]. Gasiorek A, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial. Lancet. 2025;406(10499):135-148. [Content Brief]

[4]. Khoo B, et al. GLP-1 and amylin receptor multiagonism with amycretin for obesity management[J]. The Lancet, 2025, 406(10499): 104-106.

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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.

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Zenagamtide