Benzoylhydrazide HDAC Inhibitors with Low Toxicity for Treating Cancer

Compounds Display Potent Inhibition of Cancer-Causing Enzymes and Suppression of Solid Tumor Growth

This class of small-molecule HDAC inhibitors has a novel benzoylhydrazide scaffold with potential to treat cancer, neurodegenerative disorders, and metabolic diseases. Cancer is the second leading cause of death in the United States, with more than 1.5 million people diagnosed every year. There are four HDAC inhibitors approved for cancer therapy, but those are only approved for treating hematologic malignancies such as T-cell lymphomas and multiple myelomas. Additionally, HDAC inhibitors undergoing clinical trials are continuing to face issues with dose-limiting toxicity and efficacy against solid tumors and other human diseases. Therefore, the market is in need of an HDAC inhibitor with broad therapeutic applications and low toxicity that can meet the stringent criteria for FDA approval. Researchers at the University of Florida in collaboration with scientists at the Scripps Research Institute have conducted a high-throughput screening and identified a group of benzoylhydrazide HDAC inhibitors that induces histone hyperacetylation and suppresses cancer cell proliferation. Medicinal chemistry efforts have led to optimized analogs with low nanomolar HDAC inhibition potency. Initial in vivo animal experiments show that these compounds are not toxic and exhibit good pharmacokinetic properties. These compounds are under active preclinical development for cancer therapy.

Application

HDAC inhibitor for treating cancer and other diseases (neurologic, cardiovascular, and metabolic disorders)

Advantages

• Demonstrates potential for broad therapeutic applications, offering treatment for various forms of cancer and other diseases
• Exhibits class I HDAC isoform-specificity and low toxicity, outperforming current HDAC inhibitors in clinical trials

Technology

University of Florida researchers have discovered a group of benzoylhydrazide compounds through a high-throughput screen and medicinal chemistry efforts that could potentially treat cancer, neurodegenerative disorders, and metabolic diseases. The compounds display potent in vitro inhibition of class I HDACs and inhibited cancer growth in vitro. The compounds? inhibitory activity was confirmed in cell-based assays and suppressed cancer cell proliferation of diverse cancer cell lines. In vivo animal experiments indicate that these compounds are safe and exhibit good pharmaceutical properties. The benzoylhydrazide HDAC inhibitor is currently under active preclinical development for cancer therapy.