Manipulation of hypoxia-inducible factor-1α transactivation by mutation of C-TAD residues

Hypoxia occurs when cellular oxygen demand exceeds supply. Transcriptional responses to hypoxia regulated by the hypoxia-inducible factors (HIF-1α and HIF-2α) are intimately associated with a range of pathophysiological conditions, including ischaemic disease and tumour growth. HIFs regulate the expression of a range of genes, which support tissue survival during hypoxic stress. In this patent, HIF-1α (and HIF-2α) proteins with mutated residues in the C-terminal transactivation domain (C-TAD), pivotal in transactivation, are claimed. The compounds are indicated to be used in the manipulation of HIF-dependent transcriptional control. Enhanced or inhibited HIF-activation are attractive therapeutic targets in ischaemia and cancer respectively.