Details of Drug Off-Target (DOT)

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

• DOT Name: Transcription factor E2F8 (E2F8)
• Synonyms: E2F-8
• Gene Name: E2F8
• Related Disease:
  Adult lymphoma
  Advanced cancer
  Burkitt lymphoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Estrogen-receptor positive breast cancer
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Lymphoma
  Mantle cell lymphoma
  Neoplasm
  Non-small-cell lung cancer
  Pediatric lymphoma
  Retinoblastoma
  Skin cancer
  Metastatic prostate carcinoma
  Prostate cancer
  Prostate carcinoma
  Thyroid gland papillary carcinoma
  Breast cancer
  Breast carcinoma
• UniProt ID: E2F8_HUMAN
• PDB ID: 4YO2
• Pfam ID: PF02319
• Sequence:
  MENEKENLFCEPHKRGLMKTPLKESTTANIVLAEIQPDFGPLTTPTKPKEGSQGEPWTPT
  ANLKMLISAVSPEIRNRDQKRGLFDNRSGLPEAKDCIHEHLSGDEFEKSQPSRKEKSLGL
  LCHKFLARYPNYPNPAVNNDICLDEVAEELNVERRRIYDIVNVLESLHMVSRLAKNRYTW
  HGRHNLNKTLGTLKSIGEENKYAEQIMMIKKKEYEQEFDFIKSYSIEDHIIKSNTGPNGH
  PDMCFVELPGVEFRAASVNSRKDKSLRVMSQKFVMLFLVSTPQIVSLEVAAKILIGEDHV
  EDLDKSKFKTKIRRLYDIANVLSSLDLIKKVHVTEERGRKPAFKWTGPEISPNTSGSSPV
  IHFTPSDLEVRRSSKENCAKNLFSTRGKPNFTRHPSLIKLVKSIESDRRKINSAPSSPIK
  TNKAESSQNSAPFPSKMAQLAAICKMQLEEQSSESRQKVKVQLARSGPCKPVAPLDPPVN
  AEMELTAPSLIQPLGMVPLIPSPLSSAVPLILPQAPSGPSYAIYLQPTQAHQSVTPPQGL
  SPTVCTTHSSKATGSKDSTDATTEKAANDTSKASASTRPGSLLPAPERQGAKSRTREPAG
  ERGSKRASMLEDSGSKKKFKEDLKGLENVSATLFPSGYLIPLTQCSSLGAESILSGKENS
  SALSPNHRIYSSPIAGVIPVTSSELTAVNFPSFHVTPLKLMVSPTSVAAVPVGNSPALAS
  SHPVPIQNPSSAIVNFTLQHLGLISPNVQLSASPGSGIVPVSPRIESVNVAPENAGTQQG
  RATNYDSPVPGQSQPNGQSVAVTGAQQPVPVTPKGSQLVAESFFRTPGGPTKPTSSSCMD
  FEGANKTSLGTLFVPQRKLEVSTEDVH
• Function: Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. 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: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. 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. 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.
• Reactome Pathway: TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest (R-HSA-6804116)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[3]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[5]
Lung cancer	DISCM4YA	Strong	Altered Expression	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Lymphoma	DISN6V4S	Strong	Biomarker	[1]
Mantle cell lymphoma	DISFREOV	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[8]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[1]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[9]
Skin cancer	DISTM18U	Strong	Altered Expression	[10]
Metastatic prostate carcinoma	DISVBEZ9	moderate	Altered Expression	[11]
Prostate cancer	DISF190Y	moderate	Biomarker	[11]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[11]
Thyroid gland papillary carcinoma	DIS48YMM	Disputed	Altered Expression	[12]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[13]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[13]

41 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 Transcription factor E2F8 (E2F8).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor E2F8 (E2F8).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor E2F8 (E2F8).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor E2F8 (E2F8).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor E2F8 (E2F8).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor E2F8 (E2F8).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor E2F8 (E2F8).	[20]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor E2F8 (E2F8).	[21]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Transcription factor E2F8 (E2F8).	[22]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor E2F8 (E2F8).	[23]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transcription factor E2F8 (E2F8).	[24]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor E2F8 (E2F8).	[24]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Transcription factor E2F8 (E2F8).	[25]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription factor E2F8 (E2F8).	[26]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transcription factor E2F8 (E2F8).	[27]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Transcription factor E2F8 (E2F8).	[28]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Transcription factor E2F8 (E2F8).	[29]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Transcription factor E2F8 (E2F8).	[30]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Transcription factor E2F8 (E2F8).	[31]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Transcription factor E2F8 (E2F8).	[32]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Transcription factor E2F8 (E2F8).	[33]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Transcription factor E2F8 (E2F8).	[34]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Transcription factor E2F8 (E2F8).	[35]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Transcription factor E2F8 (E2F8).	[34]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcription factor E2F8 (E2F8).	[36]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of Transcription factor E2F8 (E2F8).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor E2F8 (E2F8).	[37]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor E2F8 (E2F8).	[38]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transcription factor E2F8 (E2F8).	[39]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription factor E2F8 (E2F8).	[40]
Harmine	DMPA5WD	Patented	Harmine increases the expression of Transcription factor E2F8 (E2F8).	[42]
Nobiletin	DM7R3B6	Preclinical	Nobiletin decreases the expression of Transcription factor E2F8 (E2F8).	[43]
Oxamflatin	DM1TG3C	Terminated	Oxamflatin decreases the expression of Transcription factor E2F8 (E2F8).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Transcription factor E2F8 (E2F8).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transcription factor E2F8 (E2F8).	[30]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Transcription factor E2F8 (E2F8).	[21]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Transcription factor E2F8 (E2F8).	[11]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Transcription factor E2F8 (E2F8).	[46]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Transcription factor E2F8 (E2F8).	[47]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Transcription factor E2F8 (E2F8).	[48]
Apicidin	DM83WVF	Investigative	Apicidin decreases the expression of Transcription factor E2F8 (E2F8).	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transcription factor E2F8 (E2F8).	[41]

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