Tirzepatide 10mg

Compound Name: Tirzepatide

Synonyms: LY3298176

CAS Number: 2023788-19-2

Molecular Formula: C₂₂₅H₃₄₈N₄₈O₆₈

Molecular Weight: ~4813 Da

Molar Mass: 4705 g/mol

Structure: Synthetic 39-amino acid peptide

Peptide Sequence: His-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-Aib-Leu-Asp-Lys-Glu-Glu-Glu-Glu-Ala-Gln-Aib-Ala-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH₂

Chemical Structure:

Source: PubChem

Mechanism of Action: Tirzepatide functions as an imbalanced dual agonist of the GIP and GLP-1 receptors. It preferentially engages GIPR over GLP-1R, enhancing insulin secretion and reducing appetite. The biased agonism toward cAMP generation at the GLP-1 receptor avoids receptor internalization, contributing to increased insulinotropic effects with fewer gastrointestinal side effects at equivalent efficacy^1,3.

Biological Activity: Tirzepatide promotes glucose-dependent insulin secretion, reduces glucagon during hyperglycemia, increases satiety, reduces food intake, and lowers body weight. Clinical studies demonstrate substantial HbA1c reductions (up to −2.4%) and body weight losses exceeding 20% with high-dose regimens in people with obesity and type 2 diabetes^1,2.

Storage: −20°C or below. Protect from moisture and light.

Drug Categories: Peptide therapeutics; Incretin mimetics; Dual receptor agonists.

Additional Notes:

• Approved by FDA for type 2 diabetes; under investigation for obesity and NASH.
• Engineered for DPP-IV resistance and extended half-life via C20 fatty diacid modification.

Summary Table:

Disclaimer: For Research Use Only. Not intended for human or veterinary use. This compound is supplied solely for laboratory and R&D purposes.

Detailed Product Description

Tirzepatide is a dual incretin receptor agonist engineered to activate both GIP and GLP-1 receptors, key regulators of glycemic control and energy balance. Comprising 39 amino acids with a C20 fatty diacid side chain for half-life extension, tirzepatide is designed for once-weekly subcutaneous injection. Its receptor profile is imbalanced, favoring GIPR activation, and shows biased signaling at GLP-1R to enhance insulin secretion while minimizing receptor desensitization^2,5. Tirzepatide has demonstrated potent effects on lowering blood glucose and reducing body weight in patients with type 2 diabetes and obesity. Clinical trials have shown HbA1c reductions of up to 2.4% and body weight losses of up to 22.5%, with improvements in insulin sensitivity, lipid metabolism, and cardiometabolic markers^2,3. These effects are dose-dependent and align with its unique receptor pharmacology and optimized pharmacokinetics. Tirzepatide is currently FDA-approved for type 2 diabetes and under evaluation for obesity and metabolic liver diseases.

Research Highlights

• Superior Glycemic Control:Tirzepatide lowers HbA1c by up to 2.4% in people with type 2 diabetes, surpassing standard therapies^3,5.
• Profound Weight Loss:Up to 22.5% body weight reduction in obese individuals over 72 weeks².
• Improved Cardiometabolic Profile:Reductions in triglycerides, blood pressure, and insulin resistance (HOMA-IR) have been observed².
• Favorable Tolerability:Most adverse events are mild GI symptoms during titration^2,3,5.

Mechanism of Action

Tirzepatide exerts its dual incretin therapeutic effects through simultaneous activation of two gut hormone receptors, each contributing distinct and complementary mechanisms:

1. GIP Receptor (GIPR) Agonism

• Stimulates robust insulin secretion: GIPR activation enhances glucose-dependent insulin release from pancreatic beta cells, especially effective in the postprandial state².
• Improves lipid metabolism: Promotes lipid clearance and may support improved insulin sensitivity and adipose tissue function^1,4.
• Enhances satiety and energy balance: GIP action in the CNS contributes to reduced food intake and weight loss^1,2,3.
• Receptor binding affinity (EC₅₀, Human) = ~0.135 nM

2. GLP-1 Receptor (GLP-1R) Agonism

• Stimulates glucose-dependent insulin secretion: Enhances insulin release and lowers glucagon during hyperglycemia¹.
• Suppresses appetite (central action): Acts on hypothalamic centers to reduce hunger and increase satiety, leading to weight reduction².
• Slows gastric emptying: Delays nutrient absorption and moderates postprandial glucose excursions^1,3.
• Receptor binding affinity (EC₅₀, Human) = ~5.4 nM

Synergy of Dual Agonism

Tirzepatide’s unique imbalanced and biased receptor activation leads to synergistic enhancement of glycemic control and body weight loss beyond what is observed with GLP-1 receptor agonists alone. The combination of GIPR dominance and GLP-1R bias toward cAMP signals results in enhanced insulin secretion, improved metabolic parameters, and a more tolerable GI side effect profile^2,3,4.

Pharmacokinetic Profile:

• Route of Administration: Subcutaneous injection
• Dosing Frequency: Once weekly
• Half-Life: ~5 days
• Formulation: Lyophilized powder for reconstitution

Formulation & Handling

• Store at −20°C
• Protect from light and moisture
• Reconstitute with sterile water; avoid multiple freeze-thaw cycles

Selected Clinical Trial Activity

References

¹Willard, F.S. et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight 5, e140532 (2020). https://doi.org/10.1172/jci.insight.140532

²Rosenstock, J. et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet 398, 143–155 (2021). https://doi.org/10.1016/S0140-6736(21)01324-6

³Dahl, D. et al. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA 327, 534–545 (2022). https://doi.org/10.1001/jama.2022.0078

⁴Jastreboff, A.M. et al. Tirzepatide Once Weekly for the Treatment of Obesity. N. Engl. J. Med. 387, 205–216 (2022). https://doi.org/10.1056/NEJMoa2206038

⁵Coskun, T. et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol. Metab. 18, 3–14 (2018). https://doi.org/10.1016/j.molmet.2018.09.009