Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUQPP0R)

• DOT Name: Methyl-CpG-binding domain protein 2 (MBD2)
• Synonyms: Demethylase; DMTase; Methyl-CpG-binding protein MBD2
• Gene Name: MBD2
• Related Disease:
  Adult glioblastoma
  Bladder cancer
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Breast neoplasm
  Epithelial ovarian cancer
  Familial prostate carcinoma
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  High blood pressure
  leukaemia
  Liver cancer
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Myelodysplastic syndrome
  Neuroblastoma
  Non-small-cell lung cancer
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer, hereditary, 1
  Prostate carcinoma
  Prostate neoplasm
  Renal cell carcinoma
  Squamous cell carcinoma
  Stomach cancer
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  X-linked intellectual disability
  Rheumatoid arthritis
  Schizophrenia
  Acute myelogenous leukaemia
  Asthma
  Castration-resistant prostate carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Endometrial carcinoma
  Leukemia
  Prostate cancer
  Small-cell lung cancer
  T-cell acute lymphoblastic leukaemia
• UniProt ID: MBD2_HUMAN
• PDB ID: 2L2L; 6C1A; 6C1T; 6C1U; 6C1V; 6C2F; 6CNP; 6CNQ; 7AO8; 7AO9; 7AOA; 7MWK; 7MWM; 7RAY
• Pfam ID: PF01429 ; PF14048 ; PF16564
• Sequence:
  MRAHPGGGRCCPEQEEGESAAGGSGAGGDSAIEQGGQGSALAPSPVSGVRREGARGGGRG
  RGRWKQAGRGGGVCGRGRGRGRGRGRGRGRGRGRGRPPSGGSGLGGDGGGCGGGGSGGGG
  APRREPVPFPSGSAGPGPRGPRATESGKRMDCPALPPGWKKEEVIRKSGLSAGKSDVYYF
  SPSGKKFRSKPQLARYLGNTVDLSSFDFRTGKMMPSKLQKNKQRLRNDPLNQNKGKPDLN
  TTLPIRQTASIFKQPVTKVTNHPSNKVKSDPQRMNEQPRQLFWEKRLQGLSASDVTEQII
  KTMELPKGLQGVGPGSNDETLLSAVASALHTSSAPITGQVSAAVEKNPAVWLNTSQPLCK
  AFIVTDEDIRKQEERVQQVRKKLEEALMADILSRAADTEEMDIEMDSGDEA
• Function: Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binds hemimethylated DNA as well. Recruits histone deacetylases and DNA methyltransferases to chromatin. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Acts as a transcriptional repressor and plays a role in gene silencing. Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression. May enhance the activation of some unmethylated cAMP-responsive promoters.
• Tissue Specificity: Highly expressed in brain, heart, kidney, stomach, testis and placenta.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway:
  RNA Polymerase I Promoter Opening (R-HSA-73728)
  NoRC negatively regulates rRNA expression (R-HSA-427413)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Biomarker	[2]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Biomarker	[3]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
High blood pressure	DISY2OHH	Strong	Altered Expression	[9]
leukaemia	DISS7D1V	Strong	Biomarker	[10]
Liver cancer	DISDE4BI	Strong	Biomarker	[11]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[13]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[12]
Myelodysplastic syndrome	DISYHNUI	Strong	Posttranslational Modification	[14]
Neuroblastoma	DISVZBI4	Strong	Posttranslational Modification	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[16]
Obesity	DIS47Y1K	Strong	Altered Expression	[17]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[5]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[6]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[19]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[21]
Stomach cancer	DISKIJSX	Strong	Biomarker	[22]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[17]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]
X-linked intellectual disability	DISYJBY3	Strong	Biomarker	[23]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[24]
Schizophrenia	DISSRV2N	moderate	Biomarker	[25]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[26]
Asthma	DISW9QNS	Limited	Altered Expression	[27]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[28]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[29]
Colon cancer	DISVC52G	Limited	Biomarker	[30]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[30]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[31]
Leukemia	DISNAKFL	Limited	Altered Expression	[32]
Prostate cancer	DISF190Y	Limited	Biomarker	[18]
Small-cell lung cancer	DISK3LZD	Limited	Altered Expression	[33]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Biomarker	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[40]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the activity of Methyl-CpG-binding domain protein 2 (MBD2).	[41]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[42]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[43]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[44]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[46]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the activity of Methyl-CpG-binding domain protein 2 (MBD2).	[41]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[48]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[51]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Methyl-CpG-binding domain protein 2 (MBD2).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Methyl-CpG-binding domain protein 2 (MBD2).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Methyl-CpG-binding domain protein 2 (MBD2).	[47]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Methyl-CpG-binding domain protein 2 (MBD2).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Methyl-CpG-binding domain protein 2 (MBD2).	[50]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Methyl-CpG-binding domain protein 2 (MBD2).	[49]

References

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