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vorinostat + gemcitabine
- Development stage
- Unknown
- Lead developer
- Merck
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
Vorinostat + gemcitabine is a combination therapy investigated by the National Cancer Institute (NCI) for the treatment of advanced epithelial neoplasms. Vorinostat (also known as SAHA or Zolinza) is a small molecule histone deacetylase (HDAC) inhibitor that targets Class I, II, and IV HDAC enzymes. By inhibiting these enzymes, vorinostat increases the acetylation of histones and non-histone proteins, leading to chromatin remodeling, cell cycle arrest, and apoptosis. Gemcitabine (Gemzar) is a pyrimidine nucleoside analog that acts as an antimetabolite. It is phosphorylated intracellularly into active metabolites that inhibit DNA synthesis by incorporating into DNA and by inhibiting ribonucleotide reductase, which reduces the pool of deoxyribonucleotides available for DNA repair and synthesis. The combination has been studied in Phase 1 trials to determine the maximum tolerated dose and evaluate whether vorinostat can enhance the cytotoxic effects of gemcitabine in patients with metastatic or unresectable epithelial solid tumors.
- Brand names
- ZolinzaGemzar
- Other names
- suberoylanilide hydroxamic acidgemcitabine hydrochloride
02
Targets
HDAC6 (Histone deacetylase 6)RNR (Ribonucleotide reductase)DNA polymerase familyHDAC1 (Histone Deacetylase 1)DNAKCNH2 (Voltage-gated potassium channel subfamily H member 2)
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