This requires Flash to play. Click here to download. HDAC Inhibition and Mechanism of Action

HDAC Inhibition and Mechanism of Action
1. (Image of Tumor Cell, Tightly Coiled Chromatin and HDAC). Excess HDAC Results in Tightly Packaged DNA and Gene Silencing.

2. (Image of ZOLINZA, HDAC, Open (Uncoiled) Chromatin and Acetyl Group). HDAC Inhibition Increases Acetylation. 3. (Image of DNA, Acetyl Group, Open (Uncoiled) Chromatin, Cell-Cycle Arrest and Apoptosis). Effect on Cancer

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An oral HDAC inhibitor

HDAC inhibition and mechanism of action

This requires Flash to play. Click here to download. HDAC Inhibition and Mechanism of Action

HDAC Inhibition and Mechanism of Action
1. (Image of Tumor Cell, Tightly Coiled Chromatin and HDAC). Excess HDAC Results in Tightly Packaged DNA and Gene Silencing.

  • Histones are structural proteins around which DNA coils.
  • Excess deacetylation of histones by abnormal HDAC activity present in some tumor cells results in a closed chromatin structure, preventing DNA transcription and gene expression.
  • HDAC also has been found to deacetylate nonhistone proteins and transcription factor proteins that are involved in normal cell-cycle regulation.
2. (Image of ZOLINZA, HDAC, Open (Uncoiled) Chromatin and Acetyl Group). HDAC Inhibition Increases Acetylation.
  • ZOLINZA inhibits the enzymatic activity of histone deacetylases HDAC1 HDAC2, and HDAC3 (Class I), and HDAC6 (Class II) at nanomolar concentrations (IC50<86 nM).
  • HDAC inhibition causes increased histone acetylation, resulting in:
  • Uncoiling of DNA within chromatin
  • An open chromatin structure
  • Trascriptional activation of genes
3. (Image of DNA, Acetyl Group, Open (Uncoiled) Chromatin, Cell-Cycle Arrest and Apoptosis). Effect on Cancer
  • ZOLINZA induces cell-cycle arrest and apoptosis in some transformed cells as shown by in vitro studies.
  • The mechanism of the antineoplastic effect of ZOLINZA has not been fully characterized.


Reference: 1. Marks PA, Rifkind RA, Richon VM, Breslow R, Miller T, Kelly WK. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 2001;1:194–202.

ZOLINZA

ZOLINZA
Watch the mechanism of action video about HDAC and the effects on cancer.

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Selected Important Safety Information

  • Pulmonary embolism and deep vein thrombosis have been reported. Monitor patients for pertinent signs and symptoms, particularly in patients with a history of thromboembolic events.
  • Treatment with ZOLINZA can cause dose-related thrombocytopenia and anemia. If platelet counts and/or hemoglobin are reduced during treatment, modify the dose or discontinue therapy.
  • QTc prolongation has been observed. Monitor electrolytes and ECGs at baseline and periodically during treatment. Administer with caution in patients who have or may develop QTc prolongation. Hypokalemia or hypomagnesemia should be corrected before administering ZOLINZA.

Before prescribing ZOLINZA, please read the physician Prescribing Information. The Patient Information also is available.


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