Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6VZ78)

• DTT Name: DNA [cytosine-5]-methyltransferase 3B (DNMT3B)
• Synonyms: M.HsaIIIB; Dnmt3b; DNA methyltransferase HsaIIIB; DNA methyltransferase 3B; DNA MTase HsaIIIB; DNA (cytosine-5)-methyltransferase 3B
• Gene Name: DNMT3B
• DTT Type: Clinical trial target; [1]
• Related Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• BioChemical Class: Methyltransferase
• UniProt ID: DNM3B_HUMAN
• TTD ID: T65501
• EC Number: EC 2.1.1.37
• Sequence:
  MKGDTRHLNGEEDAGGREDSILVNGACSDQSSDSPPILEAIRTPEIRGRRSSSRLSKREV
  SSLLSYTQDLTGDGDGEDGDGSDTPVMPKLFRETRTRSESPAVRTRNNNSVSSRERHRPS
  PRSTRGRQGRNHVDESPVEFPATRSLRRRATASAGTPWPSPPSSYLTIDLTDDTEDTHGT
  PQSSSTPYARLAQDSQQGGMESPQVEADSGDGDSSEYQDGKEFGIGDLVWGKIKGFSWWP
  AMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRK
  AMYHALEKARVRAGKTFPSSPGDSLEDQLKPMLEWAHGGFKPTGIEGLKPNNTQPVVNKS
  KVRRAGSRKLESRKYENKTRRRTADDSATSDYCPAPKRLKTNCYNNGKDRGDEDQSREQM
  ASDVANNKSSLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTV
  CCEGRELLLCSNTSCCRCFCVECLEVLVGTGTAAEAKLQEPWSCYMCLPQRCHGVLRRRK
  DWNVRLQAFFTSDTGLEYEAPKLYPAIPAARRRPIRVLSLFDGIATGYLVLKELGIKVGK
  YVASEVCEESIAVGTVKHEGNIKYVNDVRNITKKNIEEWGPFDLVIGGSPCNDLSNVNPA
  RKGLYEGTGRLFFEFYHLLNYSRPKEGDDRPFFWMFENVVAMKVGDKRDISRFLECNPVM
  IDAIKVSAAHRARYFWGNLPGMNRPVIASKNDKLELQDCLEYNRIAKLKKVQTITTKSNS
  IKQGKNQLFPVVMNGKEDVLWCTELERIFGFPVHYTDVSNMGRGARQKLLGRSWSVPVIR
  HLFAPLKDYFACE
• Function: DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing. In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Function as transcriptional corepressor by associating with ZHX1. Required for DUX4 silencing in somatic cells. Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
  MicroRNAs in cancer (hsa05206)
• Reactome Pathway:
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  DNA methylation (R-HSA-5334118)
  PRC2 methylates histones and DNA (R-HSA-212300)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]

4 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID27376512-Compound-MTC-422	DM1MVQD	N. A.	N. A.	Patented	[2]
PMID27376512-Compound-MTC-423	DM9RSDX	N. A.	N. A.	Patented	[2]
PMID27376512-Compound-MTC-424	DMGNRZU	N. A.	N. A.	Patented	[2]
PMID27376512-Compound-MTC-427	DMWXEZD	N. A.	N. A.	Patented	[2]

17 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(L-)-S-adenosyl-L-homocysteine	DMDUN83	Discovery agent	N.A.	Investigative	[3], [1]
NSC-106084	DM6ID8P	Discovery agent	N.A.	Investigative	[1]
NSC-137546	DMKQYMX	Discovery agent	N.A.	Investigative	[1]
NSC-138419	DMH684Q	Discovery agent	N.A.	Investigative	[1]
NSC-154957	DMW82SA	Discovery agent	N.A.	Investigative	[1]
NSC-158324	DMDR460	Discovery agent	N.A.	Investigative	[1]
NSC-319745	DMF3G06	Discovery agent	N.A.	Investigative	[1]
NSC-345763	DM2UPSV	Discovery agent	N.A.	Investigative	[1]
NSC-348926	DM3TDEO	Discovery agent	N.A.	Investigative	[1]
NSC-401077	DM0214E	Discovery agent	N.A.	Investigative	[1]
NSC-54162	DMW2Q6N	Discovery agent	N.A.	Investigative	[1]
NSC-56071	DMLEN4X	Discovery agent	N.A.	Investigative	[1]
NSC-57893	DMIRK41	Discovery agent	N.A.	Investigative	[1]
NSC-622444	DMM5UT9	Discovery agent	N.A.	Investigative	[1]
NSC-622445	DME35CB	Discovery agent	N.A.	Investigative	[1]
NSC-623548	DMW437Z	Discovery agent	N.A.	Investigative	[1]
S-tubercidinylhomocysteine	DM9UHCY	Discovery agent	N.A.	Investigative	[4]

References

• [1] Novel and selective DNA methyltransferase inhibitors: Docking-based virtual screening and experimental evaluation. Bioorg Med Chem. 2010 Jan 15;18(2):822-9.
• [2] DNA methyltransferase inhibitors: an updated patent review (2012-2015).Expert Opin Ther Pat. 2016 Sep;26(9):1017-30.
• [3] Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors. Bioorg Med Chem Lett. 2009 May 15;19(10):2742-6.
• [4] SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes. Bioorg Med Chem Lett. 2009 May 15;19(10):2747-51.