Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM2DGTK)

• DOT Name: DNA cytosine-5)-methyltransferase 1 (DNMT1)
• Synonyms: Dnmt1; EC 2.1.1.37; CXXC-type zinc finger protein 9; DNA methyltransferase HsaI; DNA MTase HsaI; M.HsaI; MCMT
• Gene Name: DNMT1
• Related Disease:
  Autosomal dominant cerebellar ataxia, deafness and narcolepsy
  Hereditary sensory neuropathy-deafness-dementia syndrome
• UniProt ID: DNMT1_HUMAN
• PDB ID: 3EPZ; 3PTA; 3SWR; 4WXX; 4YOC; 4Z96; 4Z97; 5WVO; 5YDR; 6K3A; 6L1F; 6X9I; 6X9J; 6X9K; 7SFC; 7SFD; 7SFE; 7SFF; 7SFG; 7XI9; 7XIB
• EC Number: 2.1.1.37
• Pfam ID: PF01426 ; PF06464 ; PF00145 ; PF12047 ; PF02008
• Sequence:
  MPARTAPARVPTLAVPAISLPDDVRRRLKDLERDSLTEKECVKEKLNLLHEFLQTEIKNQ
  LCDLETKLRKEELSEEGYLAKVKSLLNKDLSLENGAHAYNREVNGRLENGNQARSEARRV
  GMADANSPPKPLSKPRTPRRSKSDGEAKPEPSPSPRITRKSTRQTTITSHFAKGPAKRKP
  QEESERAKSDESIKEEDKDQDEKRRRVTSRERVARPLPAEEPERAKSGTRTEKEEERDEK
  EEKRLRSQTKEPTPKQKLKEEPDREARAGVQADEDEDGDEKDEKKHRSQPKDLAAKRRPE
  EKEPEKVNPQISDEKDEDEKEEKRRKTTPKEPTEKKMARAKTVMNSKTHPPKCIQCGQYL
  DDPDLKYGQHPPDAVDEPQMLTNEKLSIFDANESGFESYEALPQHKLTCFSVYCKHGHLC
  PIDTGLIEKNIELFFSGSAKPIYDDDPSLEGGVNGKNLGPINEWWITGFDGGEKALIGFS
  TSFAEYILMDPSPEYAPIFGLMQEKIYISKIVVEFLQSNSDSTYEDLINKIETTVPPSGL
  NLNRFTEDSLLRHAQFVVEQVESYDEAGDSDEQPIFLTPCMRDLIKLAGVTLGQRRAQAR
  RQTIRHSTREKDRGPTKATTTKLVYQIFDTFFAEQIEKDDREDKENAFKRRRCGVCEVCQ
  QPECGKCKACKDMVKFGGSGRSKQACQERRCPNMAMKEADDDEEVDDNIPEMPSPKKMHQ
  GKKKKQNKNRISWVGEAVKTDGKKSYYKKVCIDAETLEVGDCVSVIPDDSSKPLYLARVT
  ALWEDSSNGQMFHAHWFCAGTDTVLGATSDPLELFLVDECEDMQLSYIHSKVKVIYKAPS
  ENWAMEGGMDPESLLEGDDGKTYFYQLWYDQDYARFESPPKTQPTEDNKFKFCVSCARLA
  EMRQKEIPRVLEQLEDLDSRVLYYSATKNGILYRVGDGVYLPPEAFTFNIKLSSPVKRPR
  KEPVDEDLYPEHYRKYSDYIKGSNLDAPEPYRIGRIKEIFCPKKSNGRPNETDIKIRVNK
  FYRPENTHKSTPASYHADINLLYWSDEEAVVDFKAVQGRCTVEYGEDLPECVQVYSMGGP
  NRFYFLEAYNAKSKSFEDPPNHARSPGNKGKGKGKGKGKPKSQACEPSEPEIEIKLPKLR
  TLDVFSGCGGLSEGFHQAGISDTLWAIEMWDPAAQAFRLNNPGSTVFTEDCNILLKLVMA
  GETTNSRGQRLPQKGDVEMLCGGPPCQGFSGMNRFNSRTYSKFKNSLVVSFLSYCDYYRP
  RFFLLENVRNFVSFKRSMVLKLTLRCLVRMGYQCTFGVLQAGQYGVAQTRRRAIILAAAP
  GEKLPLFPEPLHVFAPRACQLSVVVDDKKFVSNITRLSSGPFRTITVRDTMSDLPEVRNG
  ASALEISYNGEPQSWFQRQLRGAQYQPILRDHICKDMSALVAARMRHIPLAPGSDWRDLP
  NIEVRLSDGTMARKLRYTHHDRKNGRSSSGALRGVCSCVEAGKACDPAARQFNTLIPWCL
  PHTGNRHNHWAGLYGRLEWDGFFSTTVTNPEPMGKQGRVLHPEQHRVVSVRECARSQGFP
  DTYRLFGNILDKHRQVGNAVPPPLAKAIGLEIKLCMLAKARESASAKIKEEEAAKD
• Function: Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B 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. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. Promotes tumor growth.
• Tissue Specificity: Ubiquitous; highly expressed in fetal tissues, heart, kidney, placenta, peripheral blood mononuclear cells, and expressed at lower levels in spleen, lung, brain, small intestine, colon, liver, and skeletal muscle. Isoform 2 is less expressed than isoform 1.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  SUMOylation of DNA methylation proteins (R-HSA-4655427)
  DNA methylation (R-HSA-5334118)
  Defective pyroptosis (R-HSA-9710421)
  PRC2 methylates histones and DNA (R-HSA-212300)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant cerebellar ataxia, deafness and narcolepsy	DISUGGCJ	Definitive	Autosomal dominant	[1]
Hereditary sensory neuropathy-deafness-dementia syndrome	DISNXA6J	Strong	Autosomal dominant	[2]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	DNA cytosine-5)-methyltransferase 1 (DNMT1) affects the response to substance of Doxorubicin.	[50]
Cisplatin	DMRHGI9	Approved	DNA cytosine-5)-methyltransferase 1 (DNMT1) decreases the response to substance of Cisplatin.	[51]
Etoposide	DMNH3PG	Approved	DNA cytosine-5)-methyltransferase 1 (DNMT1) decreases the response to substance of Etoposide.	[51]
Hydroxyurea	DMOQVU9	Approved	DNA cytosine-5)-methyltransferase 1 (DNMT1) affects the response to substance of Hydroxyurea.	[50]
Bleomycin	DMNER5S	Approved	DNA cytosine-5)-methyltransferase 1 (DNMT1) affects the response to substance of Bleomycin.	[50]
Scopolamine	DMOM8AL	Approved	DNA cytosine-5)-methyltransferase 1 (DNMT1) increases the Memory impairment ADR of Scopolamine.	[52]

49 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[13]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[16]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[17]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[18]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[19]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[20]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[21]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[23]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[24]
Cantharidin	DMBP5N3	Approved	Cantharidin decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[25]
Fludarabine	DMVRLT7	Approved	Fludarabine decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[24]
Cladribine	DM3JDRP	Approved	Cladribine decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[24]
Magnesium	DMU4ORS	Approved	Magnesium decreases the activity of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[26]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[24]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[28]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[29]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[31]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[35]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[40]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[41]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[42]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[43]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[37]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[32]
CATECHIN	DMY38SB	Investigative	CATECHIN decreases the activity of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[26]
Myricetin	DMTV4L0	Investigative	Myricetin decreases the activity of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[26]
ROSMARINIC ACID	DMQ6SJT	Investigative	ROSMARINIC ACID decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[45]
Lefaxin	DM0CEY3	Investigative	Lefaxin decreases the expression of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[46]
(L-)-S-adenosyl-L-homocysteine	DMDUN83	Investigative	(L-)-S-adenosyl-L-homocysteine decreases the activity of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[26]
NSC-401077	DM0214E	Investigative	NSC-401077 decreases the activity of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[48]
Sinefungin	DMNWM8H	Investigative	Sinefungin decreases the activity of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[49]

7 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the methylation of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[22]
G1	DMTV42K	Phase 1/2	G1 decreases the phosphorylation of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[34]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[36]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[39]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[38]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[44]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[33]
UNC1215	DMWMRLS	Investigative	UNC1215 increases the degradation of DNA cytosine-5)-methyltransferase 1 (DNMT1).	[47]

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