2. GPCR/G Protein Protein Tyrosine Kinase/RTK
  3. Amylin Receptor GCGR Insulin Receptor
  4. Zenagamtide

Zenagamtide (Amycretin; NN 9487) is an orally active, blood-brain barrier permeable triple agonist that targets GLP-1, amylin (Amylin Receptor) and calcitonin receptor (Calcitonin Receptor). Zenagamtide 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 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 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.

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Zenagamtide

Zenagamtide Chemical Structure

CAS No. : 3005889-81-3

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Zenagamtide Related Antibodies

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Description

Zenagamtide (Amycretin; NN 9487) is an orally active, blood-brain barrier permeable triple agonist that targets GLP-1, amylin (Amylin Receptor) and calcitonin receptor (Calcitonin Receptor). Zenagamtide 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 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 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[1][2][3][4].
In Vitro

Zenagamtide activates GLP-1, amylin and calcitonin receptors in cellular systems of humans, mice and rats[1].
Zenagamtide (10-fold to 3-fold serial dilution; 30 min-3 h) potently activates human, mouse and rat GLP-1R, mouse and rat AMY3 (a)R, as well as mouse and rat CTR, with EC50 values ranging from 8.4×10-13 M to 7.8×10-11 M[2].
Zenagamtide (10-fold serial dilution; 30 min) potently activates human AMY1 (a)R, AMY2 (a)R, AMY3 (a)R, and CTR (a), with EC50 values ranging from 1.30×10-12 M to 1.72×10-11 M[2].

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

Zenagamtide Related Antibodies
In Vivo

After subcutaneous administration, Zenagamtide reduces total energy intake and body weight in diet-induced obese (DIO) rats, while improving insulin sensitivity and metabolic health markers [1].
Zenagamtide (10 nM/kg; subcutaneous injection; single dose) reduces 48-hour cumulative food intake by 50% in normal-weight male Sprague Dawley rats [2].
Zenagamtide (2-10 nM/kg; s.c.; twice daily; for 21 consecutive days) decreases total food intake by 23-30% in male DIO C57Bl/6J mice, and induces a dose-dependent, vehicle-adjusted body weight loss of 15.8-21.3% [2].
Zenagamtide (1, 3, 10 nM/kg; s.c.; once daily; for 21 consecutive days) reduces total energy intake by 47.4% in male DIO Sprague Dawley rats and achieves an 18.3% vehicle-adjusted body weight reduction while maintaining total energy expenditure [2].
Zenagamtide (1, 3, 10 nM/kg; s.c.; once daily; for 35 consecutive days) lowers HOMA-IR by 47% and increases steady-state glucose infusion rate threefold in male DIO Sprague Dawley rats, indicating improved insulin sensitivity [2].
Zenagamtide (10-30 nM/kg; s.c.; twice daily; for 12 weeks) reduces plasma liver enzyme levels, improves MASLD activity scores 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].
Fluorescently labeled Zenagamtide (100 nM/kg; i.v.; single dose) reaches key brain regions involved in energy intake regulation in male C57BL/6J mice, including circumventricular organs, the hypothalamus, and hindbrain regions [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: 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/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/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%).
Molecular Weight

7846.60

Formula

C343H550N94O116
CAS No.
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
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Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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Zenagamtide Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Zenagamtide3005889-81-3Amycretin NN 9487NN9487NN 9487NN-9487Amylin ReceptorGCGRInsulin ReceptorAMYRGlucagon ReceptorInhibitorinhibitorinhibit

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