Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTDMLNT)

• DTT Name: Hypoxia-inducible factor 2 alpha (HIF-2A)
• Synonyms: bHLHe73; PASD2; PAS domain-containing protein 2; Member of PAS protein 2; MOP2; Hypoxia-inducible factor 2-alpha; HLF; HIF2A; HIF2-alpha; HIF-2-alpha; HIF-1-alpha-like factor; Endothelial PAS domain-containing protein 1; EPAS-1; Class E basic helix-loop-helix protein 73; Basic-helix-loop-helix-PAS protein MOP2
• Gene Name: EPAS1
• DTT Type: Clinical trial target; [1]
• Related Disease: Renal cell carcinoma [ICD-11: 2C90]
• UniProt ID: EPAS1_HUMAN
• TTD ID: T21123
• Sequence:
  MTADKEKKRSSSERRKEKSRDAARCRRSKETEVFYELAHELPLPHSVSSHLDKASIMRLA
  ISFLRTHKLLSSVCSENESEAEADQQMDNLYLKALEGFIAVVTQDGDMIFLSENISKFMG
  LTQVELTGHSIFDFTHPCDHEEIRENLSLKNGSGFGKKSKDMSTERDFFMRMKCTVTNRG
  RTVNLKSATWKVLHCTGQVKVYNNCPPHNSLCGYKEPLLSCLIIMCEPIQHPSHMDIPLD
  SKTFLSRHSMDMKFTYCDDRITELIGYHPEELLGRSAYEFYHALDSENMTKSHQNLCTKG
  QVVSGQYRMLAKHGGYVWLETQGTVIYNPRNLQPQCIMCVNYVLSEIEKNDVVFSMDQTE
  SLFKPHLMAMNSIFDSSGKGAVSEKSNFLFTKLKEEPEELAQLAPTPGDAIISLDFGNQN
  FEESSAYGKAILPPSQPWATELRSHSTQSEAGSLPAFTVPQAAAPGSTTPSATSSSSSCS
  TPNSPEDYYTSLDNDLKIEVIEKLFAMDTEAKDQCSTQTDFNELDLETLAPYIPMDGEDF
  QLSPICPEERLLAENPQSTPQHCFSAMTNIFQPLAPVAPHSPFLLDKFQQQLESKKTEPE
  HRPMSSIFFDAGSKASLPPCCGQASTPLSSMGGRSNTQWPPDPPLHFGPTKWAVGDQRTE
  FLGAAPLGPPVSPPHVSTFKTRSAKGFGARGPDVLSPAMVALSNKLKLKRQLEYEEQAFQ
  DLSGGDPPGGSTSHLMWKRMKNLRGGSCPLMPDKPLSANVPNDKFTQNPMRGLGHPLRHL
  PLPQPPSAISPGENSKSRFPPQCYATQYQDYSLSSAHKVSGMASRLLGPSFESYLLPELT
  RYDCEVNVPVLGSSTLLQGGDLLRALDQAT
• Function: Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD. Transcription factor involved in the induction of oxygen regulated genes.
• Reactome Pathway:
  Cellular response to hypoxia (R-HSA-1234174)
  Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha (R-HSA-1234176)
  Transcriptional regulation of pluripotent stem cells (R-HSA-452723)
  PTK6 Expression (R-HSA-8849473)
  Neddylation (R-HSA-8951664)
  Pexophagy (R-HSA-9664873)
  Regulation of gene expression by Hypoxia-inducible Factor (R-HSA-1234158)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PT2977	DML1KTO	Renal cell carcinoma	2C90	Phase 3	[2]
PT2385	DMCSN69	Recurrent glioblastoma	2A00.00	Phase 2	[1]

References

• [1] Hypoxia-inducible factor 2: a novel target in gliomas.Future Med Chem. 2018 Sep 1;10(18):2227-2236.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)