Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWW358N)

• DOT Name: Transcription factor E2F7 (E2F7)
• Synonyms: E2F-7
• Gene Name: E2F7
• Related Disease:
  Acute myelogenous leukaemia
  Gallbladder cancer
  Thyroid gland papillary carcinoma
  Advanced cancer
  Chromosomal disorder
  Endometrial cancer
  Endometrial carcinoma
  Estrogen-receptor positive breast cancer
  Glioma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Neoplasm
  Non-small-cell lung cancer
  Ovarian neoplasm
  Skin cancer
  Squamous cell carcinoma
  Colorectal carcinoma
  Small lymphocytic lymphoma
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Gallbladder carcinoma
  Liver cancer
• UniProt ID: E2F7_HUMAN
• Pfam ID: PF02319
• Sequence:
  MEVNCLTLKDLISPRQPRLDFAVEDGENAQKENIFVDRSRMAPKTPIKNEPIDLSKQKKF
  TPERNPITPVKFVDRQQAEPWTPTANLKMLISAASPDIRDREKKKGLFRPIENKDDAFTD
  SLQLDVVGDSAVDEFEKQRPSRKQKSLGLLCQKFLARYPSYPLSTEKTTISLDEVAVSLG
  VERRRIYDIVNVLESLHLVSRVAKNQYGWHGRHSLPKTLRNLQRLGEEQKYEEQMAYLQQ
  KELDLIDYKFGERKKDGDPDSQEQQLLDFSEPDCPSSSANSRKDKSLRIMSQKFVMLFLV
  SKTKIVTLDVAAKILIEESQDAPDHSKFKTKVRRLYDIANVLTSLALIKKVHVTEERGRK
  PAFKWIGPVDFSSSDEELVDVSASVLPELKRETYGQIQVCAKQKLARHGSFNTVQASERI
  QRKVNSEPSSPYREEQGSGGYSLEIGSLAAVYRQKIEDNSQGKAFASKRVVPPSSSLDPV
  APFPVLSVDPEYCVNPLAHPVFSVAQTDLQAFSMQNGLNGQVDVSLASAASAVESLKPAL
  LAGQPLVYVPSASLFMLYGSLQEGPASGSGSERDDRSSEAPATVELSSAPSAQKRLCEER
  KPQEEDEPATKRQSREYEDGPLSLVMPKKPSDSTDLASPKTMGNRASIPLKDIHVNGQLP
  AAEEISGKATANSLVSSEWGNPSRNTDVEKPSKENESTKEPSLLQYLCVQSPAGLNGFNV
  LLSGSQTPPTVGPSSGQLPSFSVPCMVLPSPPLGPFPVLYSPAMPGPVSSTLGALPNTGP
  VNFSLPGLGSIAQLLVGPTAVVNPKSSTLPSADPQLQSQPSLNLSPVMSRSHSVVQQPES
  PVYVGHPVSVVKLHQSPVPVTPKSIQRTHRETFFKTPGSLGDPVLKRRERNQSRNTSSAQ
  RRLEIPSGGAD
• Function: Atypical E2F transcription factor that participates in various processes such as angiogenesis, polyploidization of specialized cells and DNA damage response. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1. Acts as a regulator of S-phase by recognizing and binding the E2-related site 5'-TTCCCGCC-3' and mediating repression of G1/S-regulated genes. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Also involved in DNA damage response: up-regulated by p53/TP53 following genotoxic stress and acts as a downstream effector of p53/TP53-dependent repression by mediating repression of indirect p53/TP53 target genes involved in DNA replication. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene. Acts as a negative regulator of keratinocyte differentiation.
• Reactome Pathway: TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest (R-HSA-6804116)

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Altered Expression	[1]
Gallbladder cancer	DISXJUAF	Definitive	Biomarker	[2]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[5]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[6]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[7]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Altered Expression	[8]
Glioma	DIS5RPEH	Strong	Altered Expression	[9]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[12]
Neoplasm	DISZKGEW	Strong	Altered Expression	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[13]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[14]
Skin cancer	DISTM18U	Strong	Altered Expression	[15]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[16]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[17]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[18]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[19]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[19]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[11]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[20]
Liver cancer	DISDE4BI	Limited	Biomarker	[11]

26 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 Transcription factor E2F7 (E2F7).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor E2F7 (E2F7).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor E2F7 (E2F7).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor E2F7 (E2F7).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor E2F7 (E2F7).	[25]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Transcription factor E2F7 (E2F7).	[26]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transcription factor E2F7 (E2F7).	[21]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor E2F7 (E2F7).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transcription factor E2F7 (E2F7).	[28]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor E2F7 (E2F7).	[28]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Transcription factor E2F7 (E2F7).	[29]
Marinol	DM70IK5	Approved	Marinol increases the expression of Transcription factor E2F7 (E2F7).	[30]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transcription factor E2F7 (E2F7).	[31]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Transcription factor E2F7 (E2F7).	[32]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Transcription factor E2F7 (E2F7).	[33]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Transcription factor E2F7 (E2F7).	[34]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Transcription factor E2F7 (E2F7).	[35]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription factor E2F7 (E2F7).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor E2F7 (E2F7).	[37]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription factor E2F7 (E2F7).	[39]
Harmine	DMPA5WD	Patented	Harmine increases the expression of Transcription factor E2F7 (E2F7).	[41]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transcription factor E2F7 (E2F7).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor E2F7 (E2F7).	[43]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transcription factor E2F7 (E2F7).	[44]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Transcription factor E2F7 (E2F7).	[25]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Transcription factor E2F7 (E2F7).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Transcription factor E2F7 (E2F7).	[38]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transcription factor E2F7 (E2F7).	[40]

References

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