Breakthrough HDAC6 Inhibitors for Diverse Disease Treatment

OVERVIEW

Researchers at Georgetown University have discovered compounds that are selective inhibitors of HDAC6. The proposed compounds are not hydroxamate-based, avoiding genotoxicity issues and allowing for wider drug applicability for disease indications beyond cancer. Such conditions include chemotherapy-induced cognitive impairment (CICI), Parkinson’s disease, inflammatory conditions, and others.

BACKGROUND

Inhibitors of the histone deacetylase subtype HDAC6 are known for deacetylating specific cytosolic non-histone substrates, such as heat shock protein (Hsp90), cortactin, peroxiredoxin, α-tubulin, and heat shock transcription factor 1 (HSF1). Such HDAC6is have been shown to promote α-tubulin acetylation, improve axonal transport, protect and repair peripheral axons, and overcome clinical symptoms in a host of diseases. However, currently available HDACs are not selective for specific subtypes and exhibit potential genotoxicity issues. Therefore, there is a need for HDAC inhibitors with high selectivity for the HDAC6 subtype, and reduced potential for causing genotoxicity issues.

Benefit

• Precision Targeting: these compounds demonstrate exceptional selectivity for HDAC6, unlocking the potential for tailored treatments across diverse diseases.
• The treatment of diseases wherein HDAC6 inhibition provides a benefit, such as cancers, neurological diseases, traumatic brain injury, neurodegenerative disorders and other peripheral neuropathies, stroke, hypertension, malaria, allograft rejection, rheumatoid arthritis, and various other inflammatory conditions.
• Enhanced Safety: Free from the genotoxicity risks associated with traditional inhibitors, our compounds provide a secure and reliable treatment option.

Market Application

• Compounds have the ability to treat a wide range of diseases wherein HDAC6 inhibition provides a benefit

Publications

• International Application Published WO2023154758A
• Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A. J. Am. Chem. Soc. 2010, 132, 31, 10842–10846. July 9, 2010. https://doi.org/10.1021/ja102758v