Cancer Therapeutics reveals proof of concept for second development drug
cancer therapeutics announced the validation and performance of a new targeted drug, CTx-294886, in combination with Avastin™ (bevacizumab – Genentech/Roche) in a preclinical model of breast cancer. At the same time the Company announced that it has developed a new High Throughput Screening (HTS) platform for the identification of small molecule inhibitors of protein ubiquitination, a key element in the essential cellular process of protein homeostasis, which is a new target pathway for cancer treatment.
The anti-tumour response to CTx-0294886, a potent small molecule inhibitor of Focal Adhesion Kinase (FAK) and Vascular Endothelial Growth Factor Receptor 3 (VEGFR3), was compared with that of the Company’s first product CTx-0294945, a potent selective FAK inhibitor. CTx-0294886 in combination with Avastin™, showed additional benefits to those previously demonstrated by CTx-294945 (previously presented at the AACR conference in Chicago on the 3rd of April this year). In both cases the small molecules in combination with Avastin™ inhibited angiogenesis, and increased the duration of tumour response in a model of basal breast cancer. In addition CTx-294886 in combination with Avastin™ also provided a highly statistically significant increase in the median survival time compared to the Avastin™ only group.
The new Ubiquitin HTS platform closely replicates cellular ubiquitination pathways, and provides a mechanism for HTS of multiple targets. Ubiquitins are small regulatory proteins that attach to other target proteins allowing their destruction and recycling. This process requires a family of dedicated enzymes, such as ligases, for completion. E6AP, an E3 ligase, was selected to validate the platform. E6AP ubiquitinates p53 and PML in human papilloma virus (HPV) related and other cancers. Both p53 and PML are well known suppressors of tumour growth so substances that inhibit E6AP would be expected to retard tumour growth in cancers such as cervical and head and neck cancers. The platform was able to identify several small molecules that are now undergoing further investigation.
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