Find, compare & contact
Tazemetostat API Manufacturers & Suppliers

General Description:

Tazemetostat, identified by CAS number 1403254-99-8, is a notable compound with significant therapeutic applications. Tazemetostat is a methyltransferase inhibitor used to treat metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. Tazemetostat was first named in literature as EPZ-6438. Tazemetaostat was granted FDA approval on 23 January 2020.

Indications:

This drug is primarily indicated for: Tazemetostat is indicated to treat adult and pediatric patients 16 years and older with metastatic or locally advanced epithelioid sarcoma that is not eligible for complete resection. It is also indicated to treat adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an IZH2 mutation and who have received at least 2 prior systemic therapies. Additionally, it is indicated in adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Tazemetostat undergoes metabolic processing primarily in: Tazemetostat is metabolized by CYP3A4 to an inactive desethyl metabolite and one other inactive metabolite not described. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Tazemetostat are crucial for its therapeutic efficacy: Tazemetostat 800mg twice daily leads to a C_max of 829ng/mL, with a T_max of 1-2 hours , and an AUC of 3340ng\*h/mL. Absorption is not significantly affected by a high fat, high calorie meal. Tazemetostat is 33% bioavailable. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Tazemetostat is an important consideration for its dosing schedule: Tazemetostat has a terminal elimination half life of 3.1h. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Tazemetostat exhibits a strong affinity for binding with plasma proteins: Tazemetostat is 88% 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 Tazemetostat from the body primarily occurs through: Tazemetostat is 15% eliminated in urine and 79% eliminated in feces. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Tazemetostat is distributed throughout the body with a volume of distribution of: Tazemetostat has a volume of distribution of 1230L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Tazemetostat is a critical factor in determining its safe and effective dosage: Tazemetostat has an apparent total clearance of 274L/h. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Tazemetostat exerts its therapeutic effects through: Tazemetostat is a methyltransferase inhibitor that prevents hyper-trimethylation of histones and inhibits cancer cell de-differentiation. The duration of action is long as it is given twice daily. Patients should be counselled regarding the risk of secondary malignancies and embryo-fetal toxicity. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Tazemetostat functions by: EZH2 is a methyltransferase subunit of the polycomb repressive complex 2 (PRC2) which catalyzes multiple methylations of lysine 27 on histone H3 (H3K27). Trimethylation of this lysine inhibits the transcription of genes associated with cell cycle arrest. PRC2 is antagonized by the switch/sucrose non-fermentable (SWI/SNF) multiprotein complex. Abnormal activation of EZH2 or loss of function mutations in SWI/SNF lead to hyper-trimethylation of H3K27. Hyper-trimethylation of H3K27 leads to cancer cell de-differentiation, a gain of cancer stem cell-like properties. De-differentiation can allow for cancer cell proliferation. Tazemetostat inhibits EZH2, preventing hyper-trimethylation of H3K27 and an uncontrollable cell cycle. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Tazemetostat belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond, classified under the direct parent group Biphenyls and derivatives. 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 Biphenyls and derivatives subclass.

Categories:

Tazemetostat is categorized under the following therapeutic classes: Amides, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, BCRP/ABCG2 Substrates, Benzene Derivatives, Benzoates, Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 CYP3A4 Substrates (strength unknown), Cytochrome P-450 Substrates, MATE 1 Inhibitors, MATE 2 Inhibitors, MATE 2-K Inhibitors, MATE inhibitors, Methyltransferase Inhibitor, Methyltransferase Inhibitors, Oxazines, P-glycoprotein substrates, Pyridines. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Tazemetostat include:

• logP: 2.82