TPM004
TPM004 is an ultralong-acting, nonaggregating dual amylin (AMY3R) and calcitonin receptor (CTR) agonist with EC50 values of 0.5 and 0.7 pM. TPM004 induces weight loss, attenuates adiposity rebound, lowers glucose, and improves glucose homeostasis. TPM004 can be used for the research of obesity, diabetes.
For research use only. We do not sell to patients.
- Formula: C142H227N41O47S2
- Molecular Weight:3324.70
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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]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
AMY3R 0.5 pM (EC50) |
In Vitro
TPM004 (30 min) potently activates human AMY3R in HEK-293 cells with an EC50 of 0.5 pM[1].
TPM004 (30 min) potently activates human CTR in HEK-293 cells with an EC50 of 0.7 pM[1].
TPM004 (1.0 mg/mL; 45 h) demonstrates robust resistance to fibril aggregation under physiological conditions[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | AUC0-inf | AUC0-t | T1/2 | CL | MRT0-inf | Vdss | Tmax | Cmax | F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 1.0 mg/kg | i.v. | 285.7 μg·h/mL | 285.0 μg·h/mL | 20.5 h | 3.5 mL/h/kg | 25.2 h | 0.089 L/kg | / | / | / |
| Rat[1] | 3.0 mg/kg | s.c. | 566.6 μg·h/mL | 564.4 μg·h/mL | 20.6 h | / | / | / | 24 h | 111.5 μg/mL | 66.1 % |
| Pig[1] | 0.2 mg/kg | i.v. | 253.4 μg·h/mL | 219.3 μg·h/mL | 171.3 h | 0.6 mL/h/kg | 235.0 h | 0.149 L/kg | / | / | / |
| Pig[1] | 0.2 mg/kg | s.c. | 335.1 μg·h/mL | 246.2 μg·h/mL | 243.7 h | / | / | / | 48 h | 0.87 μg/mL | 112.3 % |
| Cynomolgus Monkey[1] | 0.2 mg/kg | i.v. | 942.4 μg·h/mL | 745.6 μg·h/mL | 149.5 h | 0.2 mL/h/kg | 190.7 h | 0.041 L/kg | / | / | / |
| Cynomolgus Monkey[1] | 0.2 mg/kg | s.c. | 514.0 μg·h/mL | 402.3 μg·h/mL | 142.7 h | / | / | / | 48 h | 2.3 μg/mL | 54.5 % |
In Vivo
TPM004 (3-30 nmol/kg; s.c.; single dose) induces dose-dependent suppression of body weight gain and food intake in healthy male SD rats[1].
TPM004 (1-10 nmol/kg; s.c.; every other day; 12 days) delivers robust weight loss and food intake suppression in DIO rats[1].
TPM004 (10 nmol/kg; s.c.; every other day; 21 days) produces sustained, pronounced weight loss via selective fat reduction, improves liver health, and enhances lipid homeostasis in DIO rats[1].
TPM004 (10 nmol/kg; s.c.; every other day; 22 days) effectively lowers and stabilizes blood glucose, improves glucose tolerance, and exhibits hepatoprotective effects in ZDF rats with type 2 diabetes[1].
TPM004 (0.6-2.0 mg/kg; s.c.; twice weekly; 4 weeks) is well-tolerated with dose-dependent body weight reduction and stable pharmacokinetics in healthy male and female SD rats at supratherapeutic doses[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 mice (male, 8-10 weeks old)[1]
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Dosage:3 nmol/kg; 10 nmol/kg
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Administration:s.c.; single dose
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Result:Produced dose-dependent transient reductions in food intake and body weight.
Showed significantly attenuated body weight rebound compared to Cagrilintide (HY-P3462) at day 3 post-administration.
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Animal Model:Sprague-Dawley (SD) rats (male, 8-10 weeks old)[1]
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Dosage:3 nmol/kg; 10 nmol/kg; 30 nmol/kg
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Administration:s.c.; single dose
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Result:Elicited robust, dose-dependent suppression of body weight gain and food intake.
Produced a larger magnitude of body weight reduction than observed in mice.
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Animal Model:Diet-induced-obesity (DIO) Sprague-Dawley (SD) rats (male, 600-700 g)[1]
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Dosage:1 nmol/kg; 3 nmol/kg; 10 nmol/kg
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Administration:s.c.; every other day; 12 days
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Result:Achieved body weight and food intake reductions comparable to daily dosed Semaglutide (HY-114118) despite reduced dosing frequency, with superior efficacy at lower doses.
Showed gradual body weight and food intake rebound during post-treatment recovery on a high-fat diet, whereas Semaglutide-treated rats exhibited rapid rebound.
Produced greater body weight and food intake reductions at medium and high doses compared to Cagrilintide, with delayed rebound similar to Cagrilintide post-treatment.
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Animal Model:Zucker diabetic fatty (ZDF) rats (male, 350-400 g, type 2 diabetes model)[1]
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Dosage:10 nmol/kg
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Administration:s.c.; every other day; 22 days
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Result:Produced a marked, sustained reduction in random blood glucose, maintaining levels close to healthy controls, while vehicle-treated ZDF rats reached over 500 mg/dL.
Significantly reduced fasting blood glucose and glycated hemoglobin (HbA1c) levels, approaching those of healthy controls.
Significantly improved glucose tolerance during oral glucose tolerance test (OGTT), with a substantially lower area under the curve (AUC) compared to vehicle-treated rats.
Reduced serum ALT levels, indicating hepatoprotective effects.
Chemical Information
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Molecular Weight 3324.70
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Formula C142H227N41O47S2
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Sequence
Ac-Ala-Ser-His-Leu-Ser-Thr-Ala-Cys-Leu-Gly-Arg-Leu-Ser-Ala-Cys-Leu-His-{Lys(Me)}-Leu-Asp-Tyr-Pro-Gln-Thr-Asp-Val-Gly-Ala-Gly-Ser-{Hyp} (Disulfide bridge: Cys8-Cys15)
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Sequence Shortening
Ac-ASHLSTACLGRLSACLH-{Lys(Me)}-L-{Aib}-DYPQTDVGAGS-{Hyp} (Disulfide bridge: Cys8-Cys15)
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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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)
TPM004 Related Classifications
HY-P11843 Related Classifications
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