Description

Technical Parameters

Introduction

peptides

product-1400-1400

Products Description

#### 1. **Overview and historical background**

PT141 (Bremelanotide) is a synthetic peptide drug originally developed by Palatin Technologies in the United States. It was approved by the FDA in 2019 for the treatment of female acquired hypoactive sexual desire disorder (HSDD) under the trade name Vyleesi. Unlike traditional PDE5 inhibitors (such as sildenafil), PT141 works by activating the melanocortin receptors in the central nervous system, creating a new approach to the treatment of non-hormonal sexual dysfunction. Its research and development process began with the structural modification of α-MSH (α-melanocyte stimulating hormone), aiming to enhance receptor selectivity and improve stability.

#### 2. **Chemical structure and classification**

PT141 belongs to **cyclic heptapeptide**, with the structure of Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, molecular formula C₅₀H₆₈N₁₃O₁₀S, and molecular weight 1025.2 g/mol. Its core features include:

- **Cyclic structure**: The side chains of Asp and Lys form an intramolecular ring to enhance resistance to enzymatic hydrolysis.

- **D-amino acid modification**: The introduction of D-Phe significantly improves metabolic stability.

- **Non-natural amino acid**: Nle (norleucine) replaces natural Met to avoid oxidative degradation.

**Classification**: According to function, PT141 belongs to:

1. **Melanocortin receptor agonist** (MC4R/MC1R).

2. **Central nervous system targeting peptide**, which does not directly act on peripheral blood vessels.

3. **Therapeutic peptide drugs**, which need to be injected or administered through the nasal mucosa.

#### 3. **Pharmacological mechanism**

PT141 activates the **melanocortin receptor type 4 (MC4R)** in the hypothalamus, promotes the release of dopamine and norepinephrine, and inhibits serotonin signals, thereby enhancing sexual desire and sexual arousal. Its selectivity for MC4R is higher than MC1R (skin pigment receptor), reducing the side effect of skin pigmentation. Animal experiments show that PT141 can penetrate the blood-brain barrier, take effect within 15 minutes, and last for 8-12 hours.

#### 4. **Main advantages**

- **Fast onset**: Nasal spray takes effect in 30 minutes, and injection is faster.

- **Gender universality**: It is effective for both male and female sexual dysfunction, and the female response rate in clinical trials is about 60%.

- **Non-invasive alternative**: Nasal spray avoids injection discomfort.

- **Long-acting**: The effect of a single dose lasts for 24 hours.

- **No sexual stimulation required**: Unlike PDE5 inhibitors, the effect does not depend on physiological stimulation.

#### 5. **Physical and chemical properties**

- **Solubility**: Easily soluble in water (>50 mg/mL, pH 4-6), slightly soluble in ethanol.

- **Stability**: The activity is >90% when stored at 4℃ for 7 days in liquid state, and the lyophilized powder can be stored at -20℃ for 2 years. Sensitive to strong acid/base (easy to degrade at pH<2 or>8).

- **Synthesis process**: Solid phase peptide synthesis (SPPS) combined with oxidative cyclization, purity must be >98% (HPLC).

- **Spectral characteristics**: UV absorption peak 280 nm (Trp/His), fluorescence emission peak 350 nm.

#### 6. **Color and morphological characteristics**

- **Raw material form**: High-purity lyophilized powder is white or off-white, and may appear light gray when containing crystal water.

- **Appearance of solution**: colorless and transparent (freshly prepared), may turn slightly yellow (oxidation product) after long-term storage or exposure to light.

- **Impact influence**: Residues of synthetic intermediates may cause light pink (His oxidation product).

#### 7. **Clinical application and market**

- **Indications**: FDA approved for HSDD, with an efficacy of 65-70% for male ED in clinical trials.

- **Dosage form**: Prefilled automatic syringe (1.75 mg/0.3 mL) and nasal spray (10 mg/mL).

- **Market performance**: Global sales in 2022 will be approximately US$120 million, with North America as the main market. The price of a single dose is approximately $400, and it must be used at your own expense.

- **Competitive product comparison**: Compared with flibanserin (Addyi), PT141 has a faster onset of action and no alcohol interaction contraindications.

#### 8. **Safety and side effects**

- **Common reactions**: nausea (40%), flushing (20%), headache (10%), mostly transient.

- **Serious risks**: Transient increase in blood pressure (systolic blood pressure +10 mmHg), contraindicated in patients with uncontrolled hypertension.

- **Long-term toxicity**: No organ toxicity was found in animal experiments, but long-term data in humans is limited.

- **Drug interactions**: No contraindications with ethanol, but avoid combined use with strong CYP3A4 inhibitors.

#### 9. **Research progress and future directions**

- **New dosage forms**: Oral nanoparticles (in the preclinical stage, bioavailability increased to 15%).

- **Indication expansion**: Phase II trials show antidepressant potential (MC4R regulates mood pathways).

- **Structural optimization**: Develop analogs with higher MC4R selectivity (such as PL-8177) to reduce nausea side effects.

- **Combination therapy**: Combined with PDE5 inhibitors to treat refractory ED, with significant synergistic effects.

#### 10. **Summary and Outlook**

PT141 represents a breakthrough for peptide drugs in the field of neuroendocrinology. Its unique central mechanism and gender inclusiveness fill the gap in the sexual health market. With the advancement of delivery technology and the optimization of receptor selectivity, it is expected to expand into areas such as obesity and post-traumatic stress disorder in the future. However, the high cost and compliance issues of subcutaneous injection still need to be resolved, and the successful commercialization of oral preparations may become the next milestone.