Azacitidine

Systematic Name: 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one

Trade Name(s): Vidaza

Molecular Formula: C₈H₁₂N₄O₅

Molecular Weight: 244.20 g/mol

Physical Properties:  White to off- white powder 

Therapeutic Category: Antimetabolites, antineoplastic – Enzyme inhibitors 

The API expertise for producing Azacitidine is High Potent.

For more information about TAPI's expertise please click here

Azacitidine is used to treat myelodysplastic syndromes (MDS), a number of disorders in which not enough healthy blood cells are produced in the bone marrow, leaving patients with low blood counts. In healthy bone marrow, stem cells become red blood cells, white blood cells or platelets. In MDS, this process is dysfunctional. In a significant portion of patients, MDS progresses to a rapidly growing cancer of bone marrow cells called acute myeloid leukemia.

Administered through subcutaneous or intravenous injection, azacitidine is used for treatment of all five MDS subtypes (according to FAB classification): refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia or thrombocytopenia or requiring transfusions, refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL).

Azacitidine belongs to the class of substances termed antimetabolites. Antimetabolites are drugs that interfere with the function of enzymes involved in DNA synthesis. 

Azacitidine was approved by the FDA in 2004 under the trade name Vidaza as "the first effective treatment for patients with Myelodysplastic Syndrome (MDS)." It is designated as an orphan drug. Azacitidine is synthesized through a multi-step chemical process.

Azacitidine works both directly, destroying abnormal cells in the bone marrow, and indirectly, by intervening in genetic processes.

Genes in the DNA are not always active, but are switched on and off. DNA methylation (the addition of methyl groups to cytosine in DNA) is one of several mechanisms that cells use to control gene expression.  Too much methylation can lock genes – such as those responsible for tumor suppression or cell differentiation – in the "off" position.

Azacitidine reduces DNA methylation by posing as genetic material. It is incorporated into DNA, where it inhibits the enzyme that performs methylation (called DNA methyltransferase). This may "unlock" tumor suppressor genes as well as restore normal function to genes that are critical for differentiation. 

Azacitidine is also incorporated into RNA, disrupting normal RNA function and inhibiting protein synthesis.