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Figure 1 2.1 Structure of HIF in hypoxic microenvironment In hypoxic conditions, HIF serves as the primary signaling molecule, with HIF-1 exhibiting high sensitivity to low oxygen and serving as the core regulatory molecule in the bodys response to hypoxia ( 2 ) HIF exhibits some expression, yet the synthesized proteins undergo rapid ubiquitination and subsequent degradation via the oxygen sensor prolyl hydroxylases (PHDs)/HIF-1/pVHL pathway ( 2.2 Function of HIF in hypoxic microenvironment Under normoxia conditions, the hydroxylation of Pro402 and Pro564 residues within the ODD domain of HIF-1, catalyzed by oxygen, iron, and 2-oxoglutarate, results in conformational alterations that bolster its affinity for PHD enzyme recognition
Capsaicin ( 61 ), catalpol ( 62 ), celastrol ( 63 ), garcinol ( 64 ), huperzine ( 65 ), hydroxycitrate ( 66 ), inositol ( 67 ), naringin ( 68 ), piceatannol ( 69 ), and piperlongumine (70) (Scheme 7) [302, 303]
& Fischer, M
Hernndez-Urbn et al., 2023)
While we have learned a lot on therapeutic drug monitoring (TDM), robust biomarkers of response remain to be established
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