Teprotumumab API Manufacturers

General Description:

Teprotumumab, identified by CAS number 1036734-93-6, is a notable compound with significant therapeutic applications. Teprotumumab is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor. Following a clinical trial in which its efficacy in the treatment of thyroid eye disease (TED) was assessed, it received "breakthrough therapy" designation from the FDA in 2016 and was approved by the FDA in January 2020 for the treatment of TED. Thyroid eye disease is a potentially debilitating complication of Graves' Disease involving inflammation and tissue remodeling behind the eye, and previous treatment options typically involved multiple invasive surgeries - teprotumumab is the first drug ever approved for the treatment of TED and therefore represents a significant step forward in the treatment this disease.

Indications:

This drug is primarily indicated for: Teprotumumab is indicated for the treatment of thyroid eye disease. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Teprotumumab undergoes metabolic processing primarily in: The metabolism of teprotumumab has not been fully characterized. As a protein, its metabolism is expected to involve proteolysis to smaller proteins and peptides. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Teprotumumab are crucial for its therapeutic efficacy: In a population of 40 patients receiving standard dosing in two clinical trials of teprotumumab, utilizing a two-compartment pharmacokinetic model, the AUC and C_max were estimated to be 138 ± 34 mg•hr/mL and 632 ± 139 mcg/mL, respectively. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Teprotumumab is an important consideration for its dosing schedule: The half-life of teprotumumab is 20 ± 5 days. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Teprotumumab exhibits a strong affinity for binding with plasma proteins: Data regarding teprotumumab serum protein binding is unavailable at this time. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Teprotumumab from the body primarily occurs through: Data regarding specific route(s) of elimination are unavailable at this time. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Teprotumumab is distributed throughout the body with a volume of distribution of: Following the standard dosing regimen, the mean central and peripheral volumes of distribution are approximately 3.26 ± 0.87 L and 4.32 ± 0.67 L, respectively. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Teprotumumab is a critical factor in determining its safe and effective dosage: The estimated mean clearance of teprotumumab is 0.27 L/day. The inter-compartment clearance is 0.74 L/day. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Teprotumumab exerts its therapeutic effects through: Teprotumumab inhibits the downstream effects of IGF-1R signaling, namely tissue inflammation and remodeling, which are responsible for the various symptoms of thyroid eye disease. Teprotumumab may cause disease flares in patients with pre-existing inflammatory bowel disease (IBD) - patients experiencing an exacerbation should discontinue therapy with teprotumumab. Significant hyperglycemia has been observed in patients receiving treatment with teprotumumab which may require antihyperglycemic medications. Based on its mechanism of action, it is likely that teprotumumab will cause fetal harm in pregnant woman - for this reason, females of child-bearing age should use effective contraception prior to initiation, during therapy, and for 6 months following the last dose of teprotumumab. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Teprotumumab functions by: Graves’ Disease is an autoimmune syndrome involving the thyroid, orbital connective tissues, and some regions of the skin. One manifestation of Graves’ Disease is thyroid-associated ophthalmopathy, or thyroid eye disease, which is characterized by orbital inflammation, tissue remodeling, and fibrosis. As the disease progresses, patients may develop proptosis, strabismus, corneal ulceration, and optic neuropathy. It has been demonstrated that insulin-like growth factor-1 receptors (IGF-1R) are overexpressed by orbital fibroblasts in patients with thyroid eye disease, in addition to being overexpressed on T-cells and B-cells in these patients. It was found that Graves’ Disease IgG molecules could mimic the principal ligand of IGF-1R, insulin-like growth factor-1 (IGF-1), and their binding of IGF-1R induces the expression of chemokines that play roles in tissue remodeling and inflammation. For these reasons, IGF-1R was sought after as a potential therapeutic target for the treatment of thyroid eye disease. Teprotumumab is a fully human IgG1 monoclonal antibody directed against IGF-1R. It binds to and induces internalization and degradation of these receptors, thus preventing their downstream effects and alleviating symptoms of thyroid eye disease. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Teprotumumab belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Teprotumumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antibodies, Antineoplastic and Immunomodulating Agents, Globulins, Hyperglycemia-Associated Agents, Immunoproteins, Immunosuppressive Agents, Insulin-like Growth Factor-1 Receptor Inhibitor, Insulin-like Growth Factor-1 Receptor Inhibitors, Ototoxic agents, Proteins, Selective Immunosuppressants. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Teprotumumab include:

• Molecular Weight: 148000.0