Vorinostat

Vorinostat
Clinical data

Pronunciation	/vɒˈrɪnoʊstæt/ vorr-IN-oh-stat
Trade names	Zolinza
AHFS/Drugs.com	Monograph
MedlinePlus	a607050
License data	US FDA: Vorinostat
Pregnancy category	US: D (Evidence of risk)
Routes of administration	Oral (capsules)
ATC code	L01XX38 (WHO)
Legal status
Legal status	US: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	1.8–11%
Protein binding	~71%
Metabolism	Hepatic glucuronidation and β-oxidation system not involved
Metabolites	vorinostat O-glucuronide, 4-anilino-4-oxobutanoic acid (both inactive)
Biological half-life	~2 hours (vorinostat and O-glucuronide), 11 hours (4-anilino-4-oxobutanoic acid)
Excretion	Renal (negligible)
Identifiers
IUPAC name N-Hydroxy-N'-phenyloctanediamide
CAS Number	149647-78-9^Y
PubChem CID	5311
IUPHAR/BPS	6852
DrugBank	DB02546^Y
ChemSpider	5120^Y
UNII	58IFB293JI
KEGG	D06320^Y
ChEBI	CHEBI:45716^N
ChEMBL	CHEMBL98^Y
ECHA InfoCard	100.207.822
Chemical and physical data
Formula	C₁₄H₂₀N₂O₃
Molar mass	264.32 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(Nc1ccccc1)CCCCCCC(=O)NO
InChI InChI=1S/C14H20N2O3/c17-13(15-12-8-4-3-5-9-12)10-6-1-2-7-11-14(18)16-19/h3-5,8-9,19H,1-2,6-7,10-11H2,(H,15,17)(H,16,18)^Y Key:WAEXFXRVDQXREF-UHFFFAOYSA-N^Y
^NY (what is this?)

Vorinostat (rINN) also known as suberanilohydroxamic acid (suberoyl+anilide+hydroxamic acid abbreviated as SAHA) is a member of a larger class of compounds that inhibit histone deacetylases (HDAC). Histone deacetylase inhibitors (HDI) have a broad spectrum of epigenetic activities.

Vorinostat is marketed under the name Zolinza (/zoʊˈlɪnzə/ zoh-LIN-zə) by Merck for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) when the disease persists, gets worse, or comes back during or after two systemic therapies. The compound was developed by Columbia University chemist Ronald Breslow and Memorial Sloan-Kettering researcher Paul Marks.

Vorinostat was the first histone deacetylase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of CTCL on October 6, 2006. It also failed to demonstrate efficacy in treating acute myeloid leukemia in a phase II study.

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. 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.

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