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Studies have shown that as the oxygen gradient in solid tumors falls from 40 mmHg pO2 (5% O 2 ) in the non-hypoxic zone to 10 mmHg pO 2 (1% O 2 ) in the intermittent hypoxic (OXOPHOS) zone, PHD-2 loses its activity, whereas FIH-1 is inhibited only under severely hypoxic conditions 40 mmHg) (Figures 3), HIF-1 undergoes proteasomal degradation by PHD-2 via a process that involves post-translational hydroxylation of HIF-1 at proline residues (P402 and P564) in the human sequence present in O2 dependent degradation (ODD) domain (Schofield and Ratcliffe, 2005)

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