Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFNJ4R)

• DTT Name: Embryonic ectoderm development protein (EED)
• Synonyms: hEED; WD protein associating with integrin cytoplasmic tails 1; WAIT-1
• Gene Name: EED
• DTT Type: Clinical trial target; [1]
• UniProt ID: EED_HUMAN
• TTD ID: T44916
• Sequence:
  MSEREVSTAPAGTDMPAAKKQKLSSDENSNPDLSGDENDDAVSIESGTNTERPDTPTNTP
  NAPGRKSWGKGKWKSKKCKYSFKCVNSLKEDHNQPLFGVQFNWHSKEGDPLVFATVGSNR
  VTLYECHSQGEIRLLQSYVDADADENFYTCAWTYDSNTSHPLLAVAGSRGIIRIINPITM
  QCIKHYVGHGNAINELKFHPRDPNLLLSVSKDHALRLWNIQTDTLVAIFGGVEGHRDEVL
  SADYDLLGEKIMSCGMDHSLKLWRINSKRMMNAIKESYDYNPNKTNRPFISQKIHFPDFS
  TRDIHRNYVDCVRWLGDLILSKSCENAIVCWKPGKMEDDIDKIKPSESNVTILGRFDYSQ
  CDIWYMRFSMDFWQKMLALGNQVGKLYVWDLEVEDPHKAKCTTLTHHKCGAAIRQTSFSR
  DSSILIAVCDDASIWRWDRLR
• Function: Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A.
• Reactome Pathway:
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  PKMTs methylate histone lysines (R-HSA-3214841)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Transcriptional Regulation by E2F6 (R-HSA-8953750)
  HCMV Early Events (R-HSA-9609690)
  Defective pyroptosis (R-HSA-9710421)
  PRC2 methylates histones and DNA (R-HSA-212300)

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
MAK683	DMFK5IX	Diffuse large B-cell lymphoma	2A81	Phase 1/2	[1]
ORIC-944	DM0L8R9	Prostate cancer	2C82.0	Phase 1	[2]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-395	DMSTZ14	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] Clinical pipeline report, company report or official report of ORIC Pharmaceuticals
• [3] The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat Chem Biol. 2017 Apr;13(4):389-395.