Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOM9OE4)

• DOT Name: CCAAT/enhancer-binding protein alpha (CEBPA)
• Synonyms: C/EBP alpha
• Gene Name: CEBPA
• Related Disease: Acute myelogenous leukaemia
• UniProt ID: CEBPA_HUMAN
• PDB ID: 6DC0
• Pfam ID: PF07716
• Sequence:
  MESADFYEAEPRPPMSSHLQSPPHAPSSAAFGFPRGAGPAQPPAPPAAPEPLGGICEHET
  SIDISAYIDPAAFNDEFLADLFQHSRQQEKAKAAVGPTGGGGGGDFDYPGAPAGPGGAVM
  PGGAHGPPPGYGCAAAGYLDGRLEPLYERVGAPALRPLVIKQEPREEDEAKQLALAGLFP
  YQPPPPPPPSHPHPHPPPAHLAAPHLQFQIAHCGQTTMHLQPGHPTPPPTPVPSPHPAPA
  LGAAGLPGPGSALKGLGAAHPDLRASGGSGAGKAKKSVDKNSNEYRVRRERNNIAVRKSR
  DKAKQRNVETQQKVLELTSDNDRLRKRVEQLSRELDTLRGIFRQLPESSLVKAMGNCA
• Function: Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta. Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes. During early embryogenesis, plays essential and redundant functions with CEBPB. Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP). Critical for the proper development of the liver and the lung. Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage. To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Down-regulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters. Proliferation arrest also depends on a functional binding to SWI/SNF complex. In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC1. To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites; [Isoform 3]: Can act as dominant-negative. Binds DNA and have transctivation activity, even if much less efficiently than isoform 2. Does not inhibit cell proliferation ; [Isoform 4]: Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation.
• KEGG Pathway:
  Non-alcoholic fatty liver disease (hsa04932)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Acute myeloid leukemia (hsa05221)
• Reactome Pathway:
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of CCAAT/enhancer-binding protein alpha (CEBPA).	[2]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of CCAAT/enhancer-binding protein alpha (CEBPA).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CCAAT/enhancer-binding protein alpha (CEBPA).	[33]
MG-132	DMKA2YS	Preclinical	MG-132 increases the ubiquitination of CCAAT/enhancer-binding protein alpha (CEBPA).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of CCAAT/enhancer-binding protein alpha (CEBPA).	[36]

39 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 CCAAT/enhancer-binding protein alpha (CEBPA).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the activity of CCAAT/enhancer-binding protein alpha (CEBPA).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[11]
Marinol	DM70IK5	Approved	Marinol decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[14]
Menadione	DMSJDTY	Approved	Menadione affects the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[17]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[18]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[19]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[5]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[20]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[21]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[22]
Hesperetin	DMKER83	Approved	Hesperetin decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[23]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[24]
Sodium chloride	DMM3950	Approved	Sodium chloride increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[25]
Vitamin B3	DMQVRZH	Approved	Vitamin B3 increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[26]
Efavirenz	DMC0GSJ	Approved	Efavirenz decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[24]
Pomalidomide	DMTGBAX	Approved	Pomalidomide increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[27]
Valsartan	DMREUQ6	Approved	Valsartan decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[28]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[29]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[30]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[31]
MK-2206	DMT1OZ6	Phase 2	MK-2206 decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[34]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[35]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[37]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[38]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[39]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[40]
T0070907	DMTKSVO	Investigative	T0070907 decreases the expression of CCAAT/enhancer-binding protein alpha (CEBPA).	[18]

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