Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6RZ7VT)

• DOT Name: Transcription factor Dp-1 (TFDP1)
• Synonyms: DRTF1-polypeptide 1; DRTF1; E2F dimerization partner 1
• Gene Name: TFDP1
• Related Disease:
  Gallbladder carcinoma
  Alzheimer disease
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Cutaneous mastocytosis
  Endometriosis
  Familial adenomatous polyposis
  Hepatocellular carcinoma
  Intrahepatic cholangiocarcinoma
  Juvenile idiopathic arthritis
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-hodgkin lymphoma
  Non-small-cell lung cancer
  Retinoblastoma
  Rheumatoid arthritis
  Squamous cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Dystonia
  Glioblastoma multiforme
  Obesity
  Osteoarthritis
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal carcinoma
  Eosinophilic esophagitis
  Liver cancer
  Neoplasm
  Neoplasm of esophagus
  Van der Woude syndrome
• UniProt ID: TFDP1_HUMAN
• PDB ID: 2AZE; 5GOW; 5TUU; 5TUV
• Pfam ID: PF08781 ; PF02319
• Sequence:
  MAKDAGLIEANGELKVFIDQNLSPGKGVVSLVAVHPSTVNPLGKQLLPKTFGQSNVNIAQ
  QVVIGTPQRPAASNTLVVGSPHTPSTHFASQNQPSDSSPWSAGKRNRKGEKNGKGLRHFS
  MKVCEKVQRKGTTSYNEVADELVAEFSAADNHILPNESAYDQKNIRRRVYDALNVLMAMN
  IISKEKKEIKWIGLPTNSAQECQNLEVERQRRLERIKQKQSQLQELILQQIAFKNLVQRN
  RHAEQQASRPPPPNSVIHLPFIIVNTSKKTVIDCSISNDKFEYLFNFDNTFEIHDDIEVL
  KRMGMACGLESGSCSAEDLKMARSLVPKALEPYVTEMAQGTVGGVFITTAGSTSNGTRFS
  ASDLTNGADGMLATSSNGSQYSGSRVETPVSYVGEDDEEDDDFNENDEDD
• Function: Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members through the E2 recognition site, 5'-TTTC[CG]CGC-3', found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters.
• Tissue Specificity: Highest levels in muscle. Also expressed in brain, placenta, liver and kidney. Lower levels in lung and pancreas. Not detected in heart.
• KEGG Pathway:
  Polycomb repressive complex (hsa03083)
  Cell cycle (hsa04110)
  TGF-beta sig.ling pathway (hsa04350)
• Reactome Pathway:
  Inhibition of replication initiation of damaged DNA by RB1/E2F1 (R-HSA-113501)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)
  Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 (R-HSA-1362300)
  Activation of PUMA and translocation to mitochondria (R-HSA-139915)
  G0 and Early G1 (R-HSA-1538133)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)
  SMAD2/SMAD3 (R-HSA-2173796)
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  Oncogene Induced Senescence (R-HSA-2559585)
  TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin D associated events in G1 (R-HSA-69231)
  Cyclin A (R-HSA-69656)
  Transcriptional Regulation by E2F6 (R-HSA-8953750)
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069)
  Activation of NOXA and translocation to mitochondria (R-HSA-111448)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gallbladder carcinoma	DISD6ACL	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Cutaneous mastocytosis	DISLBZEF	Strong	Altered Expression	[5]
Endometriosis	DISX1AG8	Strong	Biomarker	[6]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[8]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[9]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[10]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[11]
Lung carcinoma	DISTR26C	Strong	Biomarker	[11]
Lung neoplasm	DISVARNB	Strong	Biomarker	[12]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Altered Expression	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[15]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[16]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[11]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Dystonia	DISJLFGW	moderate	Altered Expression	[4]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[17]
Obesity	DIS47Y1K	moderate	Biomarker	[18]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[19]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[16]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[3]
Eosinophilic esophagitis	DISR8WSB	Limited	Altered Expression	[20]
Liver cancer	DISDE4BI	Limited	Biomarker	[16]
Neoplasm	DISZKGEW	Limited	Biomarker	[3]
Neoplasm of esophagus	DISOLKAQ	Limited	Genetic Variation	[21]
Van der Woude syndrome	DISADZS1	Limited	Altered Expression	[22]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Transcription factor Dp-1 (TFDP1) affects the response to substance of DTI-015.	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Transcription factor Dp-1 (TFDP1).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor Dp-1 (TFDP1).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transcription factor Dp-1 (TFDP1).	[40]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Transcription factor Dp-1 (TFDP1).	[42]

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 Dp-1 (TFDP1).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor Dp-1 (TFDP1).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor Dp-1 (TFDP1).	[26]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Transcription factor Dp-1 (TFDP1).	[27]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription factor Dp-1 (TFDP1).	[28]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transcription factor Dp-1 (TFDP1).	[29]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor Dp-1 (TFDP1).	[30]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription factor Dp-1 (TFDP1).	[31]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Transcription factor Dp-1 (TFDP1).	[32]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Transcription factor Dp-1 (TFDP1).	[33]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Transcription factor Dp-1 (TFDP1).	[34]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Transcription factor Dp-1 (TFDP1).	[35]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Transcription factor Dp-1 (TFDP1).	[31]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Transcription factor Dp-1 (TFDP1).	[36]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Transcription factor Dp-1 (TFDP1).	[37]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Transcription factor Dp-1 (TFDP1).	[25]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the expression of Transcription factor Dp-1 (TFDP1).	[38]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Transcription factor Dp-1 (TFDP1).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Transcription factor Dp-1 (TFDP1).	[41]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Transcription factor Dp-1 (TFDP1).	[43]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Transcription factor Dp-1 (TFDP1).	[44]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Transcription factor Dp-1 (TFDP1).	[45]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Transcription factor Dp-1 (TFDP1).	[46]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Transcription factor Dp-1 (TFDP1).	[47]
acrolein	DMAMCSR	Investigative	acrolein decreases the expression of Transcription factor Dp-1 (TFDP1).	[48]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of Transcription factor Dp-1 (TFDP1).	[49]

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