ACY-1215

ACY-1215

ACY-1215, also known as ricolinostat, is a selective inhibitor of histone deacetylase 6 (HDAC6). It is primarily being investigated for its potential therapeutic applications in cancer treatment, particularly in multiple myeloma and other hematological malignancies.

Mechanism of Action

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysine residues on histone proteins, leading to chromatin condensation and transcriptional repression. HDAC6 is a unique member of the HDAC family because it primarily deacetylates non-histone proteins, such as α-tubulin and heat shock protein 90 (HSP90). By inhibiting HDAC6, ACY-1215 increases the acetylation of these proteins, which can disrupt cellular processes critical for cancer cell survival and proliferation.

Clinical Applications

1. 1. 1. Multiple Myeloma

ACY-1215 has shown promise in the treatment of multiple myeloma, a cancer of plasma cells. In preclinical studies, ACY-1215 demonstrated synergistic effects when combined with proteasome inhibitors like bortezomib. This combination enhances the accumulation of misfolded proteins in cancer cells, leading to increased cellular stress and apoptosis.

1. 1. 1. Other Hematological Malignancies

Beyond multiple myeloma, ACY-1215 is being explored for its efficacy in other blood cancers, such as lymphoma and leukemia. Its ability to modulate the immune system and enhance the activity of other anticancer agents makes it a candidate for combination therapies.

Pharmacokinetics

ACY-1215 is administered orally and has a favorable pharmacokinetic profile, with good bioavailability and a half-life that supports once-daily dosing. It is metabolized primarily in the liver and excreted in the urine.

Side Effects

The most common side effects of ACY-1215 include fatigue, gastrointestinal disturbances, and hematological toxicities such as thrombocytopenia and neutropenia. These side effects are generally manageable and reversible upon discontinuation of the drug.

Research and Development

ACY-1215 is currently undergoing clinical trials to further evaluate its safety and efficacy. Ongoing studies are focusing on its use in combination with other therapeutic agents to enhance its anticancer effects.

Also see

• Histone deacetylase inhibitors
• Multiple myeloma
• Proteasome inhibitors
• Cancer pharmacology