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HIF-1α is the sensor that lets a tumour cope with low oxygen by switching on blood-vessel growth and sugar burning. It has no direct drug yet; belzutifan hits its sibling HIF-2α, and the mTOR inhibitor temsirolimus lowers HIF-1α levels indirectly.
HIF1A (chromosome 14q23.2) encodes the oxygen-regulated subunit of hypoxia-inducible factor 1, the master transcriptional regulator of the adaptive response to hypoxia: under low oxygen it activates more than 40 genes including erythropoietin, glucose transporters, glycolytic enzymes and VEGF, heterodimerises with ARNT (HIF-1β) to bind DNA, and is essential for embryonic vascularisation, tumour angiogenesis and ischaemic disease (UniProt Q16665). The VHL/HIF pathway record explains that prolyl hydroxylases mark HIF-α for VHL-dependent destruction in normoxia and that VHL loss in most clear-cell renal cancers lets HIF-α accumulate. In OnCo, HIF-1α is named as the isoform belzutifan does not target (belzutifan stops HIF-2α dimerising with HIF-1β) and as the protein whose translation temsirolimus reduces by inhibiting mTORC1.
In plain words · HIF-1α is the sensor that lets a tumour cope with low oxygen by switching on blood-vessel growth and sugar burning. It has no direct drug yet; belzutifan hits its sibling HIF-2α, and the mTOR inhibitor temsirolimus lowers HIF-1α levels indirectly.
HIF-1α is the sensor that lets a tumour cope with low oxygen by switching on blood-vessel growth and sugar burning. It has no direct drug yet; belzutifan hits its sibling HIF-2α, and the mTOR inhibitor temsirolimus lowers HIF-1α levels indirectly.
HIF-1α and HIF-2α share the ARNT partner and many hypoxia genes; the pathway record calls HIF-2α the oncogenic paralogue in renal cell carcinoma, which is why the approved inhibitor was built for that isoform and HIF-1α remains without a direct drug in the corpus.
No product in this corpus aims at HIF-1α (HIF1A) yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
First described 1995. Earliest sequence paper UniProt cites for the protein: Wang G.L. et al, Proc. Natl. Acad. Sci. U.S.A, 1995, "Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension". Source.
HIF-1α and HIF-2α share the ARNT partner and many hypoxia genes; the pathway record calls HIF-2α the oncogenic paralogue in renal cell carcinoma, which is why the approved inhibitor was built for that isoform and HIF-1α remains without a direct drug in the corpus.
Query for this target: (TITLE:"HIF-1α" OR ABSTRACT:"HIF-1α" OR TITLE:"HIF1A" OR ABSTRACT:"HIF1A" OR TITLE:"HIF-1" OR ABSTRACT:"HIF-1" OR TITLE:"HIF-1 alpha" OR ABSTRACT:"HIF-1 alpha" OR TITLE:"HIF1" OR ABSTRACT:"HIF1" OR TITLE:"MOP1" OR ABSTRACT:"MOP1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about HIF-1α (HIF1A), not a curated reading list.
Shares VHL / HIF oxygen sensing, HIF-2α, Belzutifan, Renal cell carcinoma.
Shares mTOR, VHL / HIF oxygen sensing, HIF-2α, Cancer metabolism.
Shares VHL / HIF oxygen sensing, HIF-2α, Belzutifan, Renal cell carcinoma.
Shares Temsirolimus, mTOR, Renal cell carcinoma.
Shares Belzutifan, Clear cell renal cell carcinoma, Renal cell carcinoma.
Shares HIF-2α, Belzutifan, Renal cell carcinoma.
Shares VHL / HIF oxygen sensing, HIF-2α, The angiogenic switch & tumour vessels, VEGF / VEGFR.
Shares VHL / HIF oxygen sensing, Renal cell carcinoma (KEGG map), Clear cell renal cell carcinoma, Renal cell carcinoma.