Tumour Targeted Irreversible FGFR inhibitors
Categories for this Technology
FGFR KINASE INHIBITORS AND PHARMACEUTICAL USES
National Phase Application
A targeted approach to deliver potent irreversible FGFR inhibitors utilising hypoxia selective activation for cancer therapy.
The human fibroblast growth factor receptor (FGFR) family are a subfamily of receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4), transmembrane proteins that facilitate FGF binding and activate multiple cellular signalling cascades. FGFRs regulate important biological processes including cell growth, proliferation, differentiation and survival. Numerous human pathological conditions are associated with FGFR signal deregulation, including a variety of cancer types through FGFR gene amplification or activating mutations.
Extensive knowledge on tumour hypoxia and kinase inhibitor chemistry has resulted in the development of a novel series of potent, irreversible, FGFR1-3 inhibitors currently at lead stage. A bioreductive trigger has been identified that permits targeted release of FGFR inhibitors in the hypoxic tumour environment. The resulting prodrugs allow targeted control of FGFR gain-of-function anomalies, for therapeutic benefit at higher efficacy and with fewer off-target systemic effects.
Targeting FGFR activity has the potential to treat various cancer types where FGFR1-3 are upregulated, such as:
• Exploits hypoxic tumour environment – targeted release without the requirement to distinguish between native and cancer-driving FGFR
• Improved therapeutic window – prodrug technology results in less risk of off-target and on-mechanism toxicity, allowing more effective treatment scheduling than leading clinical FGFR inhibitors/p>
• Established technology – the bioreductive trigger that controls hypoxia-selective release has previously been evaluated in clinical trial
• Predictive biomarkers – the major contributing enzyme for inhibitor release (STEAP4) has been identified, allowing improved patient selection and response rates
Questions about this Technology?
Contact Dr Sandhya Badrinarayanan