Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWPA54)

• DTT Name: HIF2-alpha messenger RNA (EPAS1 mRNA)
• Synonyms: PASD2 mRNA; PAS domain-containing protein 2 mRNA; Member of PAS protein 2 mRNA; MOP2 mRNA; Hypoxia-inducible factor 2-alpha mRNA; HLF mRNA; HIF2A mRNA; HIF2-alpha mRNA; HIF-2-alpha mRNA; HIF-1-alpha-like factor mRNA; Endothelial PAS domain-containing protein 1 mRNA; EPAS-1 mRNA; Class E basic helix-loop-helix protein 73 mRNA; Basic-helix-loop-helix-PAS protein MOP2 mRNA; BHLHE73 mRNA
• Gene Name: EPAS1
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Adrenomedullary hyperfunction [ICD-11: 5A75]
  Brain cancer [ICD-11: 2A00]
  Renal cell carcinoma [ICD-11: 2C90]
• BioChemical Class: mRNA target
• UniProt ID: EPAS1_HUMAN
• TTD ID: T41003
• Sequence:
  MTADKEKKRSSSERRKEKSRDAARCRRSKETEVFYELAHELPLPHSVSSHLDKASIMRLA
  ISFLRTHKLLSSVCSENESEAEADQQMDNLYLKALEGFIAVVTQDGDMIFLSENISKFMG
  LTQVELTGHSIFDFTHPCDHEEIRENLSLKNGSGFGKKSKDMSTERDFFMRMKCTVTNRG
  RTVNLKSATWKVLHCTGQVKVYNNCPPHNSLCGYKEPLLSCLIIMCEPIQHPSHMDIPLD
  SKTFLSRHSMDMKFTYCDDRITELIGYHPEELLGRSAYEFYHALDSENMTKSHQNLCTKG
  QVVSGQYRMLAKHGGYVWLETQGTVIYNPRNLQPQCIMCVNYVLSEIEKNDVVFSMDQTE
  SLFKPHLMAMNSIFDSSGKGAVSEKSNFLFTKLKEEPEELAQLAPTPGDAIISLDFGNQN
  FEESSAYGKAILPPSQPWATELRSHSTQSEAGSLPAFTVPQAAAPGSTTPSATSSSSSCS
  TPNSPEDYYTSLDNDLKIEVIEKLFAMDTEAKDQCSTQTDFNELDLETLAPYIPMDGEDF
  QLSPICPEERLLAENPQSTPQHCFSAMTNIFQPLAPVAPHSPFLLDKFQQQLESKKTEPE
  HRPMSSIFFDAGSKASLPPCCGQASTPLSSMGGRSNTQWPPDPPLHFGPTKWAVGDQRTE
  FLGAAPLGPPVSPPHVSTFKTRSAKGFGARGPDVLSPAMVALSNKLKLKRQLEYEEQAFQ
  DLSGGDPPGGSTSHLMWKRMKNLRGGSCPLMPDKPLSANVPNDKFTQNPMRGLGHPLRHL
  PLPQPPSAISPGENSKSRFPPQCYATQYQDYSLSSAHKVSGMASRLLGPSFESYLLPELT
  RYDCEVNVPVLGSSTLLQGGDLLRALDQAT
• Function: Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). 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 (By similarity).
• Reactome Pathway:
  Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha (R-HSA-1234176)
  Transcriptional regulation of pluripotent stem cells (R-HSA-452723)
  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
PT2385	DMCSN69	Recurrent glioblastoma	2A00.00	Phase 2	[1]
ARO-HIF2	DMV5PEK	Renal cell carcinoma	2C90	Phase 1	[2]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 222001	DMD7HA3	Discovery agent	N.A.	Investigative	[3]
ISIS 222035	DMQY2EA	Discovery agent	N.A.	Investigative	[3]
ISIS 222039	DMVL1SN	Discovery agent	N.A.	Investigative	[3]
ISIS 222041	DMS03TR	Discovery agent	N.A.	Investigative	[3]
ISIS 222043	DM26M7E	Discovery agent	N.A.	Investigative	[3]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] National Cancer Institute Drug Dictionary (drug name ARO-HIF2).
• [3] US patent application no. 7,217,572, Modulation of HIF1.alpha. and HIF2.alpha. expression.