High Purity 99% Pharmaceutical White Powder Vorinostat CAS 149647-78-9 Anti-cancer

Vorinostat More Info

Vorinostat, also known as suberoylanilide hydroxamic acid (SAHA), is a small-molecule histone deacetylase (HDAC) inhibitor approved for the treatment of cutaneous T-cell lymphoma (CTCL).

Mechanism of Action

Vorinostat inhibits class I and II histone deacetylases (HDACs), enzymes that remove acetyl groups from lysine residues on histone and non-histone proteins. By binding to the zinc atom in the catalytic site of HDAC enzymes, vorinostat blocks their activity, leading to accumulation of acetylated histones and other proteins. This results in:
Altered chromatin structure and modulation of gene expression, including activation of tumor suppressor genes.
Induction of cell cycle arrest, differentiation, and apoptosis in cancer cells.
Inhibition of pro-growth and pro-survival signaling pathways by acetylation of transcription factors and proteins such as p53, Bcl-6, alpha-tubulin, and heat shock protein-90.
Non-transcriptional effects including inhibition of mitosis and interference with protein chaperones.
This multifaceted action disrupts tumor cell proliferation and survival.

Applications

FDA-approved indication: Treatment of cutaneous manifestations in patients with progressive, persistent, or recurrent CTCL after prior systemic therapies.
Investigational uses: Vorinostat is under clinical investigation for various hematologic malignancies and solid tumors, including prostate cancer, leukemia, breast cancer, glioma, lung cancer, diffuse large B-cell lymphoma, mesothelioma, laryngeal and thyroid tumors.
It has shown promise in preclinical and early clinical trials for these cancers, often as monotherapy or in combination with other chemotherapeutics.

Pharmacokinetics

Absorption: Vorinostat exhibits dose-proportional pharmacokinetics with modest food effects.
Protein binding: Approximately 71%.
Metabolism: Primarily metabolized via glucuronidation and hydrolysis followed by β-oxidation. Negligible cytochrome P450 involvement.
Elimination: Less than 1% excreted unchanged in urine; eliminated mainly by metabolism.
Half-life: Approximately 2 hours.
Volume of distribution and clearance: Not well defined.

Safety and Side Effects

Common Adverse Effects
Gastrointestinal: Diarrhea (45%), nausea (37%), vomiting (12%), dry mouth (16%), constipation (11%)
Hematologic: Thrombocytopenia (26%), anemia (13%)
Neurologic: Dysgeusia (23%), headache (10%), chills (11%)
Respiratory: Cough (11%), upper respiratory infection (11%)
Other: Fatigue (45%), anorexia (23%), weight loss (20%), muscle spasms (15%), peripheral edema (13%), increased creatinine (12%)
Serious Adverse Effects
Thromboembolism and deep vein thrombosis
Pulmonary embolism
Severe hematologic toxicities (more common with IV dosing)
Electrolyte imbalances
Rare but serious skin reactions
Precautions
Monitor blood counts regularly due to risk of thrombocytopenia and anemia.
Monitor for signs of infection, bleeding, and thromboembolic events.
Dose adjustments may be necessary based on toxicity.
Use with caution in patients with hepatic impairment.

Routes of Administration and Dosage

Oral administration: Vorinostat is supplied as 100 mg capsules. The approved dose is 400 mg once daily.
Dose reductions to 300 mg daily may be warranted if adverse effects occur.
Intravenous formulations have been studied (300–600 mg/m², 5 days/week for 3 weeks) but oral administration is preferred due to convenience and lower hematologic toxicity.
Treatment continues until disease progression or unacceptable toxicity.

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