Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPEO17G)

• DOT Name: Tribbles homolog 1 (TRIB1)
• Synonyms: TRB-1; G-protein-coupled receptor-induced gene 2 protein; GIG-2; SKIP1
• Gene Name: TRIB1
• Related Disease:
  Familial hypercholesterolemia
  Hypercholesterolemia, familial, 1
  Squamous cell carcinoma
  Acute leukaemia
  Acute megakaryoblastic leukemia
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Coronary atherosclerosis
  Coronary heart disease
  Epithelial recurrent erosion dystrophy
  Ewing sarcoma
  Fatty liver disease
  Glioma
  Metabolic disorder
  Myocardial ischemia
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-small-cell lung cancer
  Obesity
  Pancreatic cancer
  Prostate neoplasm
  Systemic lupus erythematosus
  Cardiovascular disease
  Hepatocellular carcinoma
  Plasma cell myeloma
  Advanced cancer
  Myocardial infarction
  Prostate cancer
  Prostate carcinoma
• UniProt ID: TRIB1_HUMAN
• PDB ID: 5CEK; 5CEM; 5IGO; 5IGQ; 6DC0
• Pfam ID: PF00069
• Sequence:
  MRVGPVRSAMSGASQPRGPALLFPATRGVPAKRLLDADDAAAVAAKCPRLSECSSPPDYL
  SPPGSPCSPQPPPAAPGAGGGSGSAPGPSRIADYLLLPLAEREHVSRALCIHTGRELRCK
  VFPIKHYQDKIRPYIQLPSHSNITGIVEVILGETKAYVFFEKDFGDMHSYVRSRKRLREE
  EAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSTEERTQLRLESLEDTHIMKGEDDALS
  DKHGCPAYVSPEILNTTGTYSGKAADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQ
  FCIPEHISPKARCLIRSLLRREPSERLTAPEILLHPWFESVLEPGYIDSEIGTSDQIVPE
  YQEDSDISSFFC
• Function: Adapter protein involved in protein degradation by interacting with COP1 ubiquitin ligase. The COP1-binding motif is masked by autoinhibitory interactions with the protein kinase domain. Serves to alter COP1 substrate specificity by directing the activity of COP1 toward CEBPA. Binds selectively the recognition sequence of CEBPA. Regulates myeloid cell differentiation by altering the expression of CEBPA in a COP1-dependent manner. Controls macrophage, eosinophil and neutrophil differentiation via the COP1-binding domain. Interacts with MAPK kinases and regulates activation of MAP kinases, but has no kinase activity.
• Tissue Specificity: Expressed in most human tissues with the highest levels in skeletal muscle, thyroid gland, pancreas, peripheral blood leukocytes, and bone marrow.
• Reactome Pathway: NGF-stimulated transcription (R-HSA-9031628)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial hypercholesterolemia	DISC06IX	Definitive	Genetic Variation	[1]
Hypercholesterolemia, familial, 1	DISU411W	Definitive	Genetic Variation	[1]
Squamous cell carcinoma	DISQVIFL	Definitive	Altered Expression	[2]
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[3]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Genetic Variation	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[8]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[8]
Epithelial recurrent erosion dystrophy	DIS2XPWB	Strong	Genetic Variation	[9]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[10]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[11]
Glioma	DIS5RPEH	Strong	Altered Expression	[12]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[5]
Myocardial ischemia	DISFTVXF	Strong	Genetic Variation	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[16]
Obesity	DIS47Y1K	Strong	Altered Expression	[17]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[18]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[19]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[5]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[20]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[21]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[22]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[6]
Myocardial infarction	DIS655KI	Limited	Genetic Variation	[23]
Prostate cancer	DISF190Y	Limited	Biomarker	[24]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[24]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Tribbles homolog 1 (TRIB1) affects the response to substance of Mitoxantrone.	[62]
Afimoxifene	DMFORDT	Phase 2	Tribbles homolog 1 (TRIB1) decreases the response to substance of Afimoxifene.	[63]

38 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 Tribbles homolog 1 (TRIB1).	[25]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tribbles homolog 1 (TRIB1).	[26]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tribbles homolog 1 (TRIB1).	[27]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tribbles homolog 1 (TRIB1).	[28]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tribbles homolog 1 (TRIB1).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tribbles homolog 1 (TRIB1).	[30]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tribbles homolog 1 (TRIB1).	[31]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tribbles homolog 1 (TRIB1).	[32]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tribbles homolog 1 (TRIB1).	[34]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tribbles homolog 1 (TRIB1).	[35]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tribbles homolog 1 (TRIB1).	[36]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tribbles homolog 1 (TRIB1).	[37]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Tribbles homolog 1 (TRIB1).	[38]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Tribbles homolog 1 (TRIB1).	[39]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Tribbles homolog 1 (TRIB1).	[40]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Tribbles homolog 1 (TRIB1).	[41]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Tribbles homolog 1 (TRIB1).	[42]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Tribbles homolog 1 (TRIB1).	[43]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Tribbles homolog 1 (TRIB1).	[44]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Tribbles homolog 1 (TRIB1).	[45]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Tribbles homolog 1 (TRIB1).	[46]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Tribbles homolog 1 (TRIB1).	[47]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Tribbles homolog 1 (TRIB1).	[48]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Tribbles homolog 1 (TRIB1).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tribbles homolog 1 (TRIB1).	[50]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tribbles homolog 1 (TRIB1).	[51]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Tribbles homolog 1 (TRIB1).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tribbles homolog 1 (TRIB1).	[53]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Tribbles homolog 1 (TRIB1).	[54]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Tribbles homolog 1 (TRIB1).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Tribbles homolog 1 (TRIB1).	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Tribbles homolog 1 (TRIB1).	[57]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tribbles homolog 1 (TRIB1).	[58]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Tribbles homolog 1 (TRIB1).	[59]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Tribbles homolog 1 (TRIB1).	[32]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Tribbles homolog 1 (TRIB1).	[60]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Tribbles homolog 1 (TRIB1).	[61]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Tribbles homolog 1 (TRIB1).	[49]

1 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 Tribbles homolog 1 (TRIB1).	[33]

References

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