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Fedratinib API Manufacturers & Suppliers

General Description:

Fedratinib, identified by CAS number 936091-26-8, is a notable compound with significant therapeutic applications. Fedratinib, also known as SAR302503 and TG101348, is a tyrosine kinase inhibitor used to treat intermediate-2 and high risk primary and secondary myelofibrosis. It is an anilinopyrimidine derivative. Fedratinib was granted FDA approval on August 16, 2019.

Indications:

This drug is primarily indicated for: Fedratinib is indicated to treat adults with primary or secondary myelofibrosis that is either intermediate-2 or high risk. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Fedratinib undergoes metabolic processing primarily in: Fedratinib is metabolized by CYP3A4, CYP2C19, and flavin-containing monooxygenase 3. Beyond that, data regarding the metabolism of fedratinib is not readily available. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Fedratinib are crucial for its therapeutic efficacy: A 400mg oral dose results in a C_max of 1804ng/mL and an AUC of 26,870ng/*hr/mL. Fedratinib has a T_max of 1.75-3 hours. A high fat breakfast does not significantly affect the absorption of fedratinib. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Fedratinib is an important consideration for its dosing schedule: The half life of fedratinib is 41 hours with a terminal half life of 114 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Fedratinib exhibits a strong affinity for binding with plasma proteins: Fedratinib is ≥92% protein bound in plasma. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Fedratinib from the body primarily occurs through: An oral dose of fedratinib is 77% eliminated in the feces with 23% as unchanged drug. 5% is eliminated in the urine, with 3% as unchanged drug. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Fedratinib is distributed throughout the body with a volume of distribution of: The apparent volume of distribution is 1770L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Fedratinib is a critical factor in determining its safe and effective dosage: The clearance of fedratinib is 13L/h. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Fedratinib exerts its therapeutic effects through: Fedratinib is a kinase inhibitor that inhibits cell division and induces apoptosis. Patients taking fedratinib may experience anemia, thrombocytopenia, gastrointestinal toxicity, hepatic toxicity, or elevated amylase and lipase. These effects should be managed by reducing the dose, temporarily stopping the medication, or providing transfusions on a case by case basis. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Fedratinib functions by: Fedratinib is an inhibitor of Janus Activated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3. JAK2 is highly active in myeloproliferative neoplasms like myelofibrosis. Fedratinib's inhibition of JAK2 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and 5, which prevents cell division and induces apoptosis. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Fedratinib belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring, classified under the direct parent group Benzenesulfonamides. This compound is a part of the Organic compounds, falling under the Benzenoids superclass, and categorized within the Benzene and substituted derivatives class, specifically within the Benzenesulfonamides subclass.

Categories:

Fedratinib is categorized under the following therapeutic classes: Amides, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, BCRP/ABCG2 Inhibitors, Cytochrome P-450 CYP2C19 Substrates, Cytochrome P-450 CYP2D6 Inhibitors, Cytochrome P-450 CYP2D6 Inhibitors (strength unknown), Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Substrates, Janus-associated kinase (JAK) inhibitors, Kinase Inhibitor, MATE 1 Inhibitors, MATE 2 Inhibitors, MATE inhibitors, OATP1B1/SLCO1B1 Inhibitors, OATP1B3 inhibitors, P-glycoprotein inhibitors, P-glycoprotein substrates, Protein Kinase Inhibitors, Sulfones, Sulfur Compounds, Tyrosine Kinase Inhibitors. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Fedratinib include:

• Water Solubility: 4µg/mL