1. Basic Information
· Generic Name: Tazemetostat
· Trade Name: Tazverik (the trade name used in the United States)
· CAS Number: 1216295-25-8
· Chemical Name: N-[(4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-5-[ethyl(tetrahydro-2H-pyran-4-yl)amino]-4-methyl-4'-(morpholin-4-yl)-[1,1'-biphenyl]-3-carboxamide
· Development Code: EPZ-6438
· Molecular Formula: C₃₄H₄₄N₄O₄
· Molecular Weight: 572.74 g/mol
2. Drug Types and Mechanisms of Action
Tazemetostat is a novel, highly selective, orally bioavailable inhibitor of EZH2.
· Target: EZH2 (Zeste gene enhancer homolog 2)
· Mechanism of action:
· EZH2 is a histone methyltransferase and it is the catalytic subunit of the polycomb repressive complex 2 (PRC2).
· The main function of EZH2 is to inhibit gene transcription by catalyzing the trimethylation of lysine at position 27 of histone H3 (H3K27me3). This is like a "gene switch" with a "off" button.
· In various cancers, EZH2 undergoes functional gain-of-function mutations or overexpression, resulting in the "incorrect" silencing of a large number of tumor suppressor genes that should normally be expressed, thereby driving the occurrence and development of tumors.
· Tazemetostat inhibits the activity of EZH2, reduces the level of H3K27me3, and reactivates these silenced tumor suppressor genes, thereby inhibiting the proliferation of tumor cells and inducing their apoptosis (programmed death).
3. Indications (Approved)
Tazemetostat has been approved by the US Food and Drug Administration (FDA) for the treatment of:
1. Epithelioid sarcoma:
· Applicable to adult and pediatric patients aged 16 and above who have inoperable metastatic or locally advanced epithelioid sarcoma.
· This is its first approved indication, representing an important therapeutic breakthrough for this rare and highly aggressive soft tissue sarcoma.
2. Follicular lymphoma:
· Applicable to adult patients with relapsed or refractory follicular lymphoma.
· Its use has an important biomarker prerequisite: the tumor must be confirmed as EZH2 mutation-positive by an FDA-approved testing method.
· For patients with EZH2 wild-type follicular lymphoma who do not have satisfactory alternative treatment options, it can also be considered for use.
4. Research and Clinical Significance
· Tazemetostat is the world's first EZH2 inhibitor approved for market by the FDA, marking a significant milestone in the field of epigenetic anti-cancer therapy.
· It has verified that EZH2 can serve as a viable target for anti-cancer drugs.
· Clinical studies targeting other cancers that rely on EZH2 (such as other types of lymphomas, sarcomas, certain solid tumors, etc.) are still being conducted extensively.
5. Common Adverse Reactions
In clinical trials, the common adverse reactions of Tazemetostat include:
· Fatigue, weakness
· Nausea, loss of appetite, constipation, vomiting
· Muscle and bone pain
· Hematological toxicities such as anemia, thrombocytopenia
· Abnormal laboratory tests (e.g., elevated aspartate aminotransferase AST, alanine aminotransferase ALT)
Serious Warning: This medication may have teratogenic effects (causing harm to the fetus). Therefore, during the period of medication use, both women of childbearing age and men should take effective contraceptive measures.
Summary
CAS 1216295-25-8 (Tazemetostat) is a landmark targeted anti-cancer drug. It treats specific advanced epithelial sarcoma and follicular lymphoma by employing an innovative epigenetic regulatory mechanism - inhibiting EZH2. This represents a significant step forward in cancer treatment, shifting from traditional chemotherapy and radiotherapy to more precise targeted therapy. It offers new hope for certain rare and refractory cancer patients.