2. GPCR/G Protein Neuronal Signaling
  3. Amylin Receptor CGRP Receptor
  4. 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.

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TPM004

TPM004 Chemical Structure

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TPM004 Related Antibodies

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Description

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[1].

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.

TPM004 Related Antibodies
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 (3-10 nmol/kg; s.c.; single dose) elicits dose-dependent, durable reductions in body weight and food intake in healthy male C57BL/6J mice[1].
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.

Animal Model: C57BL/6J mice (male, 8-10 weeks old)[1]
Dosage: 3 nmol/kg; 10 nmol/kg
Administration: s.c.; single dose
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.
Animal Model: Sprague-Dawley (SD) rats (male, 8-10 weeks old)[1]
Dosage: 3 nmol/kg; 10 nmol/kg; 30 nmol/kg
Administration: s.c.; single dose
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.
Animal Model: Diet-induced-obesity (DIO) Sprague-Dawley (SD) rats (male, 600-700 g)[1]
Dosage: 1 nmol/kg; 3 nmol/kg; 10 nmol/kg
Administration: s.c.; every other day; 12 days
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.
Animal Model: Zucker diabetic fatty (ZDF) rats (male, 350-400 g, type 2 diabetes model)[1]
Dosage: 10 nmol/kg
Administration: s.c.; every other day; 22 days
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.
Molecular Weight

3324.70

Formula

C142H227N41O47S2
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)
Sequence Shortening

Ac-ASHLSTACLGRLSACLH-{Lys(Me)}-L-{Aib}-DYPQTDVGAGS-{Hyp} (Disulfide bridge: Cys8-Cys15)
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
References
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TPM004 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:

TPM004TPM 004TPM-004Amylin ReceptorCGRP ReceptorAMYRCalcitonin gene-related peptide receptorobesitySD ratsDIO ratsdiabetesZDF ratsC57BL/6J miceHEK-293 cellstype 2 diabetescalcitonin receptoramylin receptorInhibitorinhibitorinhibit

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