Pracinostat is an investigational compound currently under study for its potential medical uses. Its development represents an ongoing effort to discover new therapeutic strategies.
What is Pracinostat
Pracinostat is an orally available, small-molecule histone deacetylase (HDAC) inhibitor. As an investigational drug, it influences specific biological processes within cells. Pracinostat is based on hydroxamic acid and has shown favorable pharmacokinetic properties.
How Pracinostat Works
Pracinostat functions by inhibiting histone deacetylase (HDAC) enzymes. These enzymes regulate gene expression by removing acetyl groups from histone proteins. When pracinostat inhibits HDACs, it leads to an accumulation of acetylated histones. This accumulation changes chromatin structure, making certain genes more accessible for transcription.
A key outcome is the selective transcription of tumor suppressor genes, which can inhibit tumor cell division and induce programmed cell death (apoptosis) in tumor cells. Pracinostat specifically inhibits HDAC class I, II, and IV enzymes, but it does not affect class III HDACs or other zinc-binding enzymes.
Conditions Pracinostat Targets
Pracinostat has shown activity in both solid tumor and hematological malignancy cell lines. It has been explored for its role in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
In preclinical models, pracinostat has demonstrated anti-tumor effects in colorectal cancer and breast cancer. It has been shown to induce cell death in colorectal cancer cells and suppress metastasis and proliferation of breast cancer cells.
Understanding Potential Side Effects
Clinical trials have reported common grade 3 or worse treatment-emergent adverse events, including infections, thrombocytopenia (low platelet count), and febrile neutropenia (fever with low white blood cell count). Fatigue is another commonly reported side effect associated with this class of drugs.
Managing these side effects often involves careful monitoring and dose adjustments or interruptions. Dose reductions or interruptions have been used in clinical studies to manage toxicities like fatigue, gastrointestinal issues, or myelosuppression. It is important to remember that individual responses to treatment can vary significantly.
Pracinostat in Clinical Trials
Pracinostat has been tested in Phase I and Phase II studies for advanced hematologic disorders and solid tumors. A Phase 1 study in patients with advanced hematologic malignancies, including AML and MDS, showed modest single-agent activity, with responses observed in some AML patients.
The combination of pracinostat with azacitidine has been a focus in later-phase trials, particularly for AML and high-risk MDS. A Phase II study in elderly AML patients ineligible for intensive chemotherapy showed a median overall survival of 19.1 months and a complete response rate of 42% with the combination. However, a Phase III trial investigating pracinostat with azacitidine in newly diagnosed AML patients was discontinued after an interim analysis indicated it was unlikely to meet its primary endpoint of overall survival. Despite this, the combination received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for AML, and Breakthrough Therapy Designation from the FDA.