Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN9VHAG)

• DOT Name: Homeobox protein TGIF1 (TGIF1)
• Synonyms: 5'-TG-3'-interacting factor 1
• Gene Name: TGIF1
• Related Disease:
  Alobar holoprosencephaly
  Holoprosencephaly 5
  Lobar holoprosencephaly
  Neoplasm
  Acute myelogenous leukaemia
  Colonic neoplasm
  Colorectal neoplasm
  Diabetic kidney disease
  Fetal growth restriction
  Holoprosencephaly
  Holoprosencephaly 4
  Hyperlipidemia, familial combined, LPL related
  Intellectual disability
  Intestinal neoplasm
  Matthew-Wood syndrome
  Moyamoya disease
  Non-small-cell lung cancer
  Otitis media
  Pancreatic ductal carcinoma
  Polydactyly
  Acute otitis media
  Chronic otitis media
  Hypotrichosis simplex
  Pulmonary disease
  Rheumatoid arthritis
  Neural tube defect
  Advanced cancer
  Metastatic malignant neoplasm
  Pancreatic cancer
  Psychotic disorder
• UniProt ID: TGIF1_HUMAN
• PDB ID: 2LK2; 6FQP; 6FQQ
• Pfam ID: PF05920
• Sequence:
  MVLAQSRVSAGVGSPHCSGSGGGGSDSFPWPASHPGNPQCSFSTAFLASPRLSRGTLAYL
  PPAPWSSLATPSALLGSSCAPPPPPARCPQPRALSPELGTKAGPRRPHRWELPRSPSQGA
  QGPAPRRRLLETMKGIVAASGSETEDEDSMDIPLDLSSSAGSGKRRRRGNLPKESVQILR
  DWLYEHRYNAYPSEQEKALLSQQTHLSTLQVCNWFINARRRLLPDMLRKDGKDPNQFTIS
  RRGAKISETSSVESVMGIKNFMPALEETPFHSCTAGPNPTLGRPLSPKPSSPGSVLARPS
  VICHTTVTALKDVPFSLCQSVGVGQNTDIQQIAAKNFTDTSLMYPEDTCKSGPSTNTQSG
  LFNTPPPTPPDLNQDFSGFQLLVDVALKRAAEMELQAKLTA
• Function: Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. Active transcriptional corepressor of SMAD2. Links the nodal signaling pathway to the bifurcation of the forebrain and the establishment of ventral midline structures. May participate in the transmission of nuclear signals during development and in the adult, as illustrated by the down-modulation of the RXR alpha activities.
• KEGG Pathway: TGF-beta sig.ling pathway (hsa04350)
• Reactome Pathway:
  SMAD2/SMAD3 (R-HSA-2173796)
  Downregulation of SMAD2/3 (R-HSA-2173795)

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alobar holoprosencephaly	DISON1K9	Definitive	Biomarker	[1]
Holoprosencephaly 5	DIS2AK05	Definitive	Autosomal dominant	[2]
Lobar holoprosencephaly	DISVK1YW	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[5]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[6]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[7]
Fetal growth restriction	DIS5WEJ5	Strong	Altered Expression	[8]
Holoprosencephaly	DISR35EC	Strong	Biomarker	[9]
Holoprosencephaly 4	DISJIY0R	Strong	Autosomal dominant	[10]
Hyperlipidemia, familial combined, LPL related	DISL1CE3	Strong	Biomarker	[11]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[12]
Intestinal neoplasm	DISK0GUH	Strong	Altered Expression	[5]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[13]
Moyamoya disease	DISO62CA	Strong	Genetic Variation	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Otitis media	DISGZDUO	Strong	Biomarker	[15]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Biomarker	[13]
Polydactyly	DIS25BMZ	Strong	Biomarker	[16]
Acute otitis media	DISL8D8G	moderate	Genetic Variation	[15]
Chronic otitis media	DIS3P3TG	moderate	Genetic Variation	[15]
Hypotrichosis simplex	DIS8WHDJ	moderate	Genetic Variation	[17]
Pulmonary disease	DIS6060I	moderate	Biomarker	[18]
Rheumatoid arthritis	DISTSB4J	moderate	Altered Expression	[19]
Neural tube defect	DIS5J95E	Disputed	Genetic Variation	[20]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[13]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[13]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[13]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Homeobox protein TGIF1 (TGIF1).	[22]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Homeobox protein TGIF1 (TGIF1).	[23]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Homeobox protein TGIF1 (TGIF1).	[24]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Homeobox protein TGIF1 (TGIF1).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Homeobox protein TGIF1 (TGIF1).	[26]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Homeobox protein TGIF1 (TGIF1).	[27]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Homeobox protein TGIF1 (TGIF1).	[28]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Homeobox protein TGIF1 (TGIF1).	[29]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Homeobox protein TGIF1 (TGIF1).	[30]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Homeobox protein TGIF1 (TGIF1).	[31]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Homeobox protein TGIF1 (TGIF1).	[32]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Homeobox protein TGIF1 (TGIF1).	[33]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Homeobox protein TGIF1 (TGIF1).	[19]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Homeobox protein TGIF1 (TGIF1).	[24]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Homeobox protein TGIF1 (TGIF1).	[35]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Homeobox protein TGIF1 (TGIF1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Homeobox protein TGIF1 (TGIF1).	[37]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Homeobox protein TGIF1 (TGIF1).	[38]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Homeobox protein TGIF1 (TGIF1).	[39]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Homeobox protein TGIF1 (TGIF1).	[40]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Homeobox protein TGIF1 (TGIF1).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Homeobox protein TGIF1 (TGIF1).	[42]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Homeobox protein TGIF1 (TGIF1).	[43]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Homeobox protein TGIF1 (TGIF1).	[44]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Homeobox protein TGIF1 (TGIF1).	[45]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Homeobox protein TGIF1 (TGIF1).	[46]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Homeobox protein TGIF1 (TGIF1).	[47]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Homeobox protein TGIF1 (TGIF1).	[48]

References

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