Citarinostat

Citarinostat (also known by its research code ACY-241) is a novel small molecule inhibitor of histone deacetylases (HDACs), specifically targeting class I and IIb HDACs. It is being investigated for its potential use in the treatment of various cancers, including multiple myeloma and solid tumors.

Mechanism of Action

Citarinostat functions by inhibiting the activity of histone deacetylases, which are enzymes that remove acetyl groups from lysine residues on histone proteins. This action leads to an open chromatin structure and increased transcriptional activity of genes that can induce cell cycle arrest, differentiation, and apoptosis in cancer cells. By targeting specific HDACs, citarinostat aims to modulate gene expression in a way that suppresses tumor growth and enhances the efficacy of other anticancer therapies.

Clinical Development

Citarinostat is currently undergoing clinical trials to evaluate its safety and efficacy in combination with other anticancer agents. Early-phase clinical trials have shown promising results, particularly in combination with immunomodulatory drugs and proteasome inhibitors in the treatment of multiple myeloma. The drug is being developed by Acetylon Pharmaceuticals, a subsidiary of Celgene Corporation.

Pharmacokinetics

The pharmacokinetic profile of citarinostat includes oral bioavailability, with studies indicating a favorable absorption and distribution pattern. The drug is metabolized primarily in the liver and excreted via the renal and fecal routes. The half-life of citarinostat supports once-daily dosing, which is advantageous for patient compliance.

Adverse Effects

Common adverse effects observed in clinical trials include fatigue, nausea, diarrhea, and thrombocytopenia. These side effects are generally manageable and consistent with those observed with other HDAC inhibitors. Ongoing studies aim to further elucidate the safety profile of citarinostat, particularly in combination regimens.

Research Directions

Research is ongoing to explore the full potential of citarinostat in various cancer types. Preclinical studies suggest that it may also enhance the immune response against tumors, making it a candidate for combination with immune checkpoint inhibitors. Additionally, its role in epigenetic modulation is being investigated to understand its broader applications in oncology.

Also see

• Histone deacetylase inhibitor
• Multiple myeloma
• Epigenetic therapy
• Cancer immunotherapy