Hypoxia Inducible Factors

Hypoxia Inducible Factors (HIFs) are transcription factors that are activated in response to decreased oxygen availability in the cellular environment. They influence cell metabolism, cell survival and angiogenesis to maintain biological homeostasis.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
5953 Adaptaquin
HIF-prolyl hydroxylase-2 (PHD2) inhibitor; antioxidant
5582 TAT-cyclo-CLLFVY
Selective HIF-1 dimerization inhibitor
4408 DMOG
Inhibitor of hypoxia-inducible factor α (HIF-α) prolyl hydroxylase (HIF-PH)
5520 Echinomycin
Highly potent and selective HIF-1α inhibitor
5655 GN 44028
Potent HIF-1α inhibitor
4451 IOX 2
Potent, selective HIF-1α prolyl hydroxylase-2 (PHD2) inhibitor
4324 KC7F2
HIF-1α inhibitor; down-regulates HIF-1α protein synthesis
2954 PX 12
Thioredoxin-1 inhibitor; attenuates expression of HIF-1α
5243 TC-S 7009
High affinity and selective HIF-2α inhibitor
6156 VH 298
High-affinity inhibitor of VHL

Activators

Cat No Product Name / Activity
4565 ML 228
HIF pathway activator

Other

Cat No Product Name / Activity
4705 Chetomin
Blocks interaction of HIF-1α, HIF-2α and STAT2 with CBP/p300
6155 cis MZ 1
Negative Control for MZ1
6157 cis VH 298
Negative control for VH 298
5764 Deferoxamine mesylate
Hypoxia mimetic; also iron chelator
6154 MZ 1
(+)-JQ1 based PROTAC that selectively degrades BRD4 in cells

Related Targets

    Hypoxia Inducible Factors (HIFs) are transcription factors that are activated in response to decreased oxygen availability in the cellular environment. They influence cell metabolism, cell survival and angiogenesis to maintain biological homeostasis. The HIF family is made up of α subunits (HIF-1, HIF-2 and HIF-3) and a constitutively expressed β subunit (ARNT; also known as Aryl hydrocarbon Receptor Nuclear Translocator).

    The best characterized hypoxia response pathway is mediated by hypoxia-inducible factor-1 (HIF-1). In normoxia (when oxygen is present), prolyl hydroxylases 1-3 (PHD1-3) control the degradation of HIF-1α through hydroxylating several proline residues located at the oxygen-dependent degradation domain of HIF-1α. Hydroxylated HIF-1α interacts with von Hippel-Lindau (VHL) protein targeting it for proteasomal degradation. In hypoxia (the absence of oxygen), the HIFα subunit is stabilized due to the lack of oxygen; it translocates to the nucleus, where it dimerizes with the nuclear HIF-1β (ARNT) to form the transcriptionally active HIF. By interacting with the co-activator CBP/p300, HIF-1 activates transcription of target genes that fall into four major categories: glucose transporters and glycolysis, angiogenesis, survival and proliferation, as well as invasion and metastasis. HIF-2α appears to also be regulated by this mechanism; however, HIF-3α may have a different role in the inhibition of HIF-1α and HIF-2α. HIF thereby regulates gene expression through interaction with specific hypoxic response elements (HRE) on hypoxic responsive genes.

    HIF-1α has been shown to play an important role in the tumor response to hypoxia. Hypoxia increases tumor glycolysis, angiogenesis and other survival responses, as well as invasion and metastasis, by activating relevant genes through HIFs. HIF-1α activity in tumors has been correlated with increased angiogenesis and aggressive tumor growth, and therefore has led to current interest in HIF-1α as a pharmacological target within cancer research.

    Hypoxia also induces epigenetic changes in chromatin architecture and DNA methylation status, and HIF-1α has also been suggested to regulate several histone demethylase enzymes.

    Literature for Hypoxia Inducible Factors

    Cancer

    Cancer Research Product Guide

    A collection of over 750 products for cancer research, the guide includes research tools for the study of:

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    Angiogenesis in Cancer

    Angiogenesis in Cancer Poster

    Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the pathogenesis of angiogenesis in cancer, as well as some of the main angiogenesis therapeutic targets.

    Hypoxia Inducible Factor Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    Hypoxia Inducible Factor 1, alpha subunit Human HIF1A NM_001530 Q16665
    Mouse Hif1a NM_010431 Q61221
    Rat Hif1a NM_024359 O35800
    Hypoxia Inducible Factor 1, alpha subunit inhibitor Human HIF1AN NM_017902 Q9NWT6
    Mouse Hif1an NM_176958 Q8BLR9
    Rat Hif1an NM_001113749 B0BNG5
    Hypoxia Inducible Factor 3, alpha subunit Human HIF3A NM_152796 Q9Y2N7
    Mouse Hif3a NM_016868 Q0VBL6
    Rat Hif3a NM_022528 Q9JHS2
    Aryl hydrocarbon Receptor Nuclear Translocator
    (ARNT, HIF-1β)
    Human ARNT NM_001197325 P27540
    Mouse Arnt NM_001037737 P53762
    Rat Arnt NM_012780 P41739
    Endothelial PAS domain protein 1
    (EPAS, HIF2A)
    Human EPAS1 NM_001430 Q99814
    Mouse Epas1 NM_010137 P97481
    Rat Epas1 NM_023090 Q9JHS1
    SET domain containing 2 (HIF-1) Human SETD2 NM_014159 Q9BYW2
    Mouse Setd2 NM_001081340 E9Q5F9
    Rat Setd2 NM_001108189 D4AA96