Vorinostat is a histone deacetylase inhibitor used as a medicine in the treatment of T-cell lymphoma.
| Vorinostat | |
|---|---|
 | |
| Chemical compound | |
| IUPAC | N -hydroxy- N '-phenyl-octanediamide |
| Gross formula | C 14 H 20 N 2 O 3 |
| Molar mass | 264.32 g / mol |
| Cas | |
| PubChem | |
| Drugbank | |
| Classification | |
| ATX | |
| Pharmacokinetics | |
| Plasma Protein Binding | 71% |
| Metabolism | Hepatic glucuronidation and oxidation CYP system not involved |
| The half-life. | 2 hours |
| Excretion | Renal (negligible) |
| Route of administration | |
| Oral | |
Vorinostat is manufactured and sold by Merck under the trade name 'Zolinza' as a drug for the treatment of skin manifestations in patients with T-cell lymphoma, which has a progressive, persistent or relapsing character during systemic therapy, the dosage form is tablets containing 100 mg of the active substance.
As of 2016, the price of the drug in the US was $ 94.54 per pill, or $ 11,362.30 per pack of 120 tablets for a monthly course of therapy [1]
The compound was developed by Columbia University chemist Dr. Ronald Breslow .
Mechanism of Action
Vorinostat is an inhibitor of class I zinc-containing histone deacetylases ( HDAC1 , HDAC2 and HDAC3 ) and class II HDAC6 histone deacetylases, but not class III histone deacetylases.
Inhibition occurs due to the coordination of the hydroxam group with the zinc atom of the enzyme reaction center with simultaneous blocking of the catalytic pocket by the phenyl group [2] .
Inhibition of histone deacetylases (with constant activity of histone acetyltransferases ) leads to the accumulation of an increase in the proportion of acetylated histones in chromatin , which is an important factor in maintaining pluripotency and differentiation of cells [3] , and thereby suppressing malignant growth.
Literature
- ↑ Zolinza 100 mg Price Comparisons - Online Pharmacies and Discount Coupons . Date of treatment October 3, 2016.
- ↑ Richon, Victoria Cancer biology: mechanism of antitumour action of vorinostat (suberoylanilide hydroxamic acid), a novel histone deacetylase inhibitor . British Journal of Cancer. Date of treatment May 3, 2012.
- ↑ Guang Hu, Paul A. Wade (2012) NuRD and Pluripotency: A Complex Balancing Act , 10 (5), 497-503 https://dx.doi.org/10.1016/j.stem.2012.04.01.01