CXD101: A novel HDAC inhibitor
CXD101 is a novel histone deacetylase (HDAC) inhibitor with multiple positive differentiation properties from competing products which is supported by a biomarker identified by CancerNav™. Now in clinical trials.
Major advances in elucidating the complexity of chromatin and its role in the epigenetic regulation of eukaryotic gene expression have been achieved. An excellent understanding of chromatin control and the enzymatic modifications that impart diverse regulatory cues on the functional activity of the genome is now available. Most importantly, chromatin research has uncovered a large body of information that is being harnessed in developing new therapeutics for cancer.
HDAC, which regulates the acetylation level of chromatin, has proved to be a very attractive cancer target. Small molecule HDAC inhibitors in clinical trials exhibit anti-cancer activity, although their precise clinical utility remains to be determined. Many existing rationally designed HDAC inhibitors exhibit toxicity that precludes clinical development and the tumour types that will undergo a favourable response to HDAC inhibitors are not known.
Celleron’s novel HDAC inhibitor, CXD101, has been acquired from AstraZeneca. CXD101 offers a compelling opportunity for clinical development, and has superior properties and multiple positive differentiation properties compared to any of the other competing HDAC inhibitors in clinical development.
Most importantly, Celleron has used CancerNav™ to identify a response biomarker for CXD101. CancerNav™ identified a single biomarker that regulates tumour cell sensitivity to HDAC inhibitors.
Currently, there is intense interest in HDAC as a therapeutic target. However, for most HDAC inhibitors the clinical picture, particularly responsive tumours, is not clear. In order to overcome this bottleneck, Celleron used CancerNav to identify genes that confer sensitivity to HDAC inhibitors. A single biomarker for HDAC inhibitor responsive tumours has been validated in the clinical setting, focussing on the ability to identify responsive tumours.
Evidence that the biomarker provides useful information on the clinical outcome of HDAC inhibitor-based therapy has been provided by studying cutaneous T cell lymphoma (CTCL), which to date is the only tumour for which HDAC inhibitors have been approved (Zolinza/SAHA in October 2006). The HDAC inhibitor biomarker is expressed at high levels in the malignant T cells in CTCL biopsies.
Further screening of a repository of human tumour biopsies identified the HDAC inhibitor biomarker at high levels in certain types of cancer. This information has been incorporated into to the clinical development plan for CXD101.
HDAC, which regulates the acetylation level of chromatin, has proved to be a very attractive cancer target. Small molecule HDAC inhibitors in clinical trials exhibit anti-cancer activity, although their precise clinical utility remains to be determined. Many existing rationally designed HDAC inhibitors exhibit toxicity that precludes clinical development and the tumour types that will undergo a favourable response to HDAC inhibitors are not known.
Celleron’s novel HDAC inhibitor, CXD101, has been acquired from AstraZeneca. CXD101 offers a compelling opportunity for clinical development, and has superior properties and multiple positive differentiation properties compared to any of the other competing HDAC inhibitors in clinical development.
Most importantly, Celleron has used CancerNav™ to identify a response biomarker for CXD101. CancerNav™ identified a single biomarker that regulates tumour cell sensitivity to HDAC inhibitors.
Currently, there is intense interest in HDAC as a therapeutic target. However, for most HDAC inhibitors the clinical picture, particularly responsive tumours, is not clear. In order to overcome this bottleneck, Celleron used CancerNav to identify genes that confer sensitivity to HDAC inhibitors. A single biomarker for HDAC inhibitor responsive tumours has been validated in the clinical setting, focussing on the ability to identify responsive tumours.
Evidence that the biomarker provides useful information on the clinical outcome of HDAC inhibitor-based therapy has been provided by studying cutaneous T cell lymphoma (CTCL), which to date is the only tumour for which HDAC inhibitors have been approved (Zolinza/SAHA in October 2006). The HDAC inhibitor biomarker is expressed at high levels in the malignant T cells in CTCL biopsies.
Further screening of a repository of human tumour biopsies identified the HDAC inhibitor biomarker at high levels in certain types of cancer. This information has been incorporated into to the clinical development plan for CXD101.