Hypoxia activated inhibitors
Tumour cells rapidly proliferate at a rate that is poorly supported by the vascular architecture resulting in regions of cells exceeding the diffusible limits of oxygen. The resulting hypoxia is a hallmark of cancer and has been associated with several important features including: resistance to ionising radiation first reported in the seminal work of Thomlinson & Gray (1), the magnification of mutated p53 (2) and the activation of the transcription factor hypoxia-inducible factor-1 (HIF-1) (3).
Sentinel Oncology is developing small molecule inhibitors that are inert until activated by the low oxygen regions found in solid tumours. Our inhibitors within this class are designed to have a broad spectrum of activity once activated in the tumour.
(1) Thomlinson, R.H.; Gray, L.H. Br. J. Cancer, 1955, 9, 539-549
(2) Graeber T.G.; Osmanian C.; Jacks T.; Housman D.E.; Koch C.J.; Lowe S.W.; Glaccia A.J. Nature, 1996, 379, 88-91
(3) Bardos, J.I.; Ashcroft, M. Biochim Biophys Acta., 2005,;1755(2), 107-120