Vorinostat
Clinical data | |
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Pronunciation | /vɒˈrɪnoʊstæt/ vorr-IN-oh-stat |
Trade names | Zolinza |
AHFS/Drugs.com | Monograph |
MedlinePlus | a607050 |
License data |
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Routes of administration | Oral (capsules) |
ATC code | |
Legal status | |
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CYP system not involved | |
Metabolites | vorinostat O-glucuronide, 4-anilino-4-oxobutanoic acid (both inactive)[2] |
Elimination half-life | ~2 hours (vorinostat and O-glucuronide), 11 hours (4-anilino-4-oxobutanoic acid) |
Excretion | Renal (negligible) |
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Vorinostat (
Vorinostat is marketed under the name Zolinza (
Medical uses
Vorinostat was the first histone deacetylase inhibitor[7] approved by the U.S. Food and Drug Administration (FDA) for the treatment of CTCL on October 6, 2006.[8]
Development
In 1966, Charlotte Friend published her observation that a suspension of murine erythroleukemia cells underwent cytodifferentiation to normal erythrocytes when treated with dimethylsulfoxide (DMSO, a common drug solvent and cryoprotectant frequently used for cell culture freezing) at 280 mmolar.[9][10] Memorial Sloan-Kettering researcher Paul Marks approached Columbia University chemist Ronald Breslow about these findings and together they decided to develop more potent analogs of DMSO, in order to make use of this property for cancer treatment. Their optimization process lead to the discovery of suberoylanilide hydroxamic acid and its HDAC-inhibiting property.[6][11]
Mechanism of action
Vorinostat has been shown to bind to the active site of histone deacetylases and act as a chelator for zinc ions also found in the active site of histone deacetylases.[12] Vorinostat's inhibition of histone deacetylases results in the accumulation of acetylated histones and acetylated proteins, including transcription factors crucial for the expression of genes needed to induce cell differentiation.[12] It acts on class I, II and IV of histone deacetylase.
Clinical trials
Vorinostat has also been used to treat
A recent study suggested that vorinostat also possesses some activity against recurrent
Including vorinostat in treatment of advanced
It has given encouraging results in a phase II trial[16] for myelodysplastic syndromes in combination with idarubicin and cytarabine.[17] It failed to demonstrate efficacy in treating acute myeloid leukemia in an earlier phase II study.[18]
Preclinical investigations
Vorinostat is being investigated as a potential HIV latency reversing agent (LRA) as part of an investigational therapeutic strategy known as "shock and kill".[19] Vorinostat was shown to reactivate HIV in latently HIV-infected T cells, both in vitro and in vivo.[20][21]
Vorinostat also has shown some activity against the pathophysiological changes in
Recent evidence also suggests vorinostat can be a therapeutic tool for Niemann-Pick type C1 (NPC1), a rare lysosomal lipid storage disease.[24]Preclinical experiments by University of Alabama at Birmingham researchers suggest the cancer drugs vorinostat, belinostat and panobinostat might be repurposed to treat infections caused by human papillomavirus, or HPV.[25]
See also
References
- ^ "Withdrawal Assessment Report for Vorinostat MSD 100 mg Hard Capsules (vorinostat)" (PDF). European Medicines Agency. 23 October 2008. p. 9. Retrieved 1 September 2016.
- ^ a b "Zolinza (vorinostat) Capsules. Full Prescribing Information" (PDF). Merck & Co., Inc., Whitehouse Station, NJ 08889, USA. Retrieved 1 September 2016.
- ^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 56" (PDF). WHO Drug Information. 20 (3): 232. 2006. Archived from the original (PDF) on July 5, 2011. Retrieved 1 September 2016.
- ^ "ZOLINZA, Merck's Investigational Medicine for Advanced Cutaneous T-Cell Lymphoma (CTCL), To Receive Priority Review from U.S. Food and Drug Administration" (Press release). Merck & Co. June 7, 2006. Archived from the original on September 14, 2006. Retrieved October 6, 2006.
- PMID 24023063.
- ^ S2CID 12656582.
- ^ "Vorinostat". HDAC Inhibitors Base.
- ^ "Zolinza (vorinostat) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 16 February 2014.
- PMID 5923328.
- PMID 5277089.
- ISBN 978-3-527-80031-5. Retrieved 2022-11-18.
- ^ PMID 16307490.
- ^ Castoldi G, Cuneo A (May 2005). "Mycosis fungoides/Sezary's syndrome". Atlas of Genetics and Cytogenetics in Oncology and Haematology. Retrieved 2008-02-15.
- ^ "Vorinostat shows anti-cancer activity in recurrent gliomas" (Press release). Mayo Clinic. June 3, 2007. Retrieved 2007-06-03.
- PMID 19933908.
- PMID 22585696.
- ^ Langholtz J, Haehle M (11 January 2012). "Zolinza, Idarubicin, Cytarabine Combination Yields High Response Rates In MDS Patients (ASH 2011)". The MDS Beacon. Archived from the original on 2014-10-30. Retrieved 2012-01-17.
- PMID 19794082.
- ^ Clinical trial number NCT01319383 for "The Effect of Vorinostat on HIV RNA Expression in the Resting CD4+ T Cells of HIV+ Pts on Stable ART" at ClinicalTrials.gov
- PMID 19239360.
- PMID 19136668.
- PMID 22995909.
- PMID 19966789.
- S2CID 5762569.
- ^ "Cancer drug may help treat human papillomavirus infections". ScienceDaily. 30 November 2018. Retrieved 2018-11-30.
External links
- Vorinostat bound to proteins in the PDB