Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJW2UQ)

• DTT Name: EZH2 Y641N mutant (EZH2 Y641N)
• Synonyms: Lysine Nmethyltransferase 6 Y641N mutant; Lysine N-methyltransferase 6 Y641N mutant; KMT6 Y641N mutant; Histonelysine Nmethyltransferase EZH2 Y641N mutant; Histone-lysine N-methyltransferase EZH2 Y641N mutant; EZH2 Y641N mutations; ENX1 Y641N mutant; ENX-1 Y641N mutant
• Gene Name: EZH2
• DTT Type: Patented-recorded target; [1]
• UniProt ID: EZH2_HUMAN
• TTD ID: T04980
• EC Number: EC 2.1.1.43
• Sequence:
  MGQTGKKSEKGPVCWRKRVKSEYMRLRQLKRFRRADEVKSMFSSNRQKILERTEILNQEW
  KQRRIQPVHILTSVSSLRGTRECSVTSDLDFPTQVIPLKTLNAVASVPIMYSWSPLQQNF
  MVEDETVLHNIPYMGDEVLDQDGTFIEELIKNYDGKVHGDRECGFINDEIFVELVNALGQ
  YNDDDDDDDGDDPEEREEKQKDLEDHRDDKESRPPRKFPSDKIFEAISSMFPDKGTAEEL
  KEKYKELTEQQLPGALPPECTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFLHPFH
  ATPNTYKRKNTETALDNKPCGPQCYQHLEGAKEFAAALTAERIKTPPKRPGGRRRGRLPN
  NSSRPSTPTINVLESKDTDSDREAGTETGGENNDKEEEEKKDETSSSSEANSRCQTPIKM
  KPNIEPPENVEWSGAEASMFRVLIGTYYDNFCAIARLIGTKTCRQVYEFRVKESSIIAPA
  PAEDVDTPPRKKKRKHRLWAAHCRKIQLKKDGSSNHVYNYQPCDHPRQPCDSSCPCVIAQ
  NFCEKFCQCSSECQNRFPGCRCKAQCNTKQCPCYLAVRECDPDLCLTCGAADHWDSKNVS
  CKNCSIQRGSKKHLLLAPSDVAGWGIFIKDPVQKNEFISEYCGEIISQDEADRRGKVYDK
  YMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIGIFAKRAIQTGE
  ELFFDYRYSQADALKYVGIEREMEIP
• Function: Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2. Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. 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, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription. Polycomb group (PcG) protein.
• KEGG Pathway:
  Lysine degradation (hsa00310)
  Metabolic pathways (hsa01100)
  MicroRNAs in cancer (hsa05206)
• 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)
• BioCyc Pathway: MetaCyc:HS02911-MON

Molecular Interaction Atlas (MIA) of This DTT

5 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID28394193-Compound-45	DMZJXPF	N. A.	N. A.	Patented	[1]
PMID28394193-Compound-46	DMYMPNA	N. A.	N. A.	Patented	[1]
PMID28394193-Compound-55	DM2FPHZ	N. A.	N. A.	Patented	[1]
PMID28394193-Compound-56	DMQRFZK	N. A.	N. A.	Patented	[1]
PMID28394193-Compound-57	DM4Y3US	N. A.	N. A.	Patented	[1]

References

• [1] EZH2 inhibitors: a patent review (2014-2016).Expert Opin Ther Pat. 2017 Jul;27(7):797-813.