2. Academic Validation
  3. Targeting hypoxia-inducible factors: therapeutic opportunities and challenges

Targeting hypoxia-inducible factors: therapeutic opportunities and challenges

  • Nat Rev Drug Discov. 2024 Mar;23(3):175-200. doi: 10.1038/s41573-023-00848-6.
Xiaoyi Yuan 1,  Wei Ruan 2 3,  Bentley Bobrow 4,  Peter Carmeliet 5 6 7,  Holger K Eltzschig 8 9
Affiliations

Affiliations

  • 1 Department of Anaesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. [email protected].
  • 2 Department of Anaesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • 3 Department of Anaesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China.
  • 4 Department of Emergency Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • 5 Laboratory of Angiogenesis & Vascular Metabolism, Center for Cancer Biology, VIB, Department of Oncology, KU Leuven, Leuven, Belgium.
  • 6 Laboratory of Angiogenesis & Vascular Heterogeneity, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  • 7 Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
  • 8 Department of Anaesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. [email protected].
  • 9 Outcomes Research Consortium, Cleveland, OH, USA. [email protected].
PMID: 38123660 DOI: 10.1038/s41573-023-00848-6
Abstract

Hypoxia-inducible factors (HIFs) are highly conserved transcription factors that are crucial for adaptation of metazoans to limited oxygen availability. Recently, HIF activation and inhibition have emerged as therapeutic targets in various human diseases. Pharmacologically desirable effects of HIF activation include erythropoiesis stimulation, cellular metabolism optimization during hypoxia and adaptive responses during ischaemia and inflammation. By contrast, HIF inhibition has been explored as a therapy for various cancers, retinal neovascularization and pulmonary hypertension. This Review discusses the biochemical mechanisms that control HIF stabilization and the molecular strategies that can be exploited pharmacologically to activate or inhibit HIFs. In addition, we examine medical conditions that benefit from targeting HIFs, the potential side effects of HIF activation or inhibition and future challenges in this field.

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