Karus Therapeutics Extends Drug Discovery Programme to Target HDAC-6
News Feb 22, 2010
Karus Therapeutics Ltd, a company engaged in the discovery and development of molecular-targeted drugs to treat inflammation and cancer, announced that it had extended its HDAC drug discovery programme to include small molecules that selectively inhibit HDAC-6, a target of emerging importance in the treatment of immune-inflammatory disorders.
The Company says that it has recently designed and developed a novel series of highly potent and selective HDAC-6 inhibitors which display excellent anti-inflammatory activity, notably in preclinical models of Rheumatoid Arthritis, and which have additional potential across a wide range of immune-inflammatory disorders.
Until recently, the development of HDAC inhibitors has been focused mainly on the treatment of cancer. However, there is a growing body of evidence from preclinical in vitro and in vivo models that the inhibition of HDAC-6 leads to increased expression of the FOXP3 transcription factor, a protein which plays a key role in the development and immunosuppressive function of regulatory T-cells in the context of chronic diseases such as Rheumatoid Arthritis, Psoriasis, Multiple Sclerosis, Lupus and Organ Transplant Rejection.
“There is a significant opportunity for the development of an important new class of anti-inflammatory drugs which selectively target HDAC-6.” said Karus Therapeutics CEO Simon Kerry “While HDAC inhibitors have been predominantly developed for use in oncology, our selective inhibitors of HDAC-6 have important anti-inflammatory and immunosuppressive qualities, which should translate into the effective treatment of a wide number of inflammatory indications and post-transplantation procedures.”
CSO Stephen Shuttleworth said: “The discovery and development of HDAC inhibitors with high levels of HDAC-6 selectivity has historically proven to be extremely challenging; there is currently a dearth of drug-like isoform-specific inhibitors and, therefore, a great demand for such molecules. We believe that the subtype-selective inhibitors developed at Karus represent a truly unique series of small molecule therapeutics with great potential in the treatment of chronic inflammatory diseases.”
HDAC-6 has also recently emerged as an important drug target in neurodegenerative disorders, including Alzheimer's Disease (AD), as well as stroke and spinal cord injury, and selective HDAC-6 inhibitors are expected to show promise as neuroprotectants in AD and related neurodegenerative diseases. Karus is currently undertaking additional proof-of-concept studies to assess the potential of its new class of HDAC-6 selective inhibitors in this clinical setting.