Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM9MQIA)

• DOT Name: CCAAT/enhancer-binding protein beta (CEBPB)
• Synonyms: C/EBP beta; Liver activator protein; LAP; Liver-enriched inhibitory protein; LIP; Nuclear factor NF-IL6; Transcription factor 5; TCF-5
• Gene Name: CEBPB
• UniProt ID: CEBPB_HUMAN
• PDB ID: 1GTW; 1GU4; 1GU5; 1H88; 1H89; 1H8A; 1HJB; 1IO4; 2E42; 2E43; 6MG1; 6MG2; 6MG3; 7L4V; 7UPZ
• Pfam ID: PF07716
• Sequence:
  MQRLVAWDPACLPLPPPPPAFKSMEVANFYYEADCLAAAYGGKAAPAAPPAARPGPRPPA
  GELGSIGDHERAIDFSPYLEPLGAPQAPAPATATDTFEAAPPAPAPAPASSGQHHDFLSD
  LFSDDYGGKNCKKPAEYGYVSLGRLGAAKGALHPGCFAPLHPPPPPPPPPAELKAEPGFE
  PADCKRKEEAGAPGGGAGMAAGFPYALRAYLGYQAVPSGSSGSLSTSSSSSPPGTPSPAD
  AKAPPTACYAGAAPAPSQVKSKAKKTVDKHSDEYKIRRERNNIAVRKSRDKAKMRNLETQ
  HKVLELTAENERLQKKVEQLSRELSTLRNLFKQLPEPLLASSGHC
• Function: Important transcription factor regulating the expression of genes involved in immune and inflammatory responses. Also plays a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant roles with CEBPA. Has a promitotic effect on many cell types such as hepatocytes and adipocytes but has an antiproliferative effect on T-cells by repressing MYC expression, facilitating differentiation along the T-helper 2 lineage. Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation. Also plays a role in intracellular bacteria killing. During adipogenesis, is rapidly expressed and, after activation by phosphorylation, induces CEBPA and PPARG, which turn on the series of adipocyte genes that give rise to the adipocyte phenotype. The delayed transactivation of the CEBPA and PPARG genes by CEBPB appears necessary to allow mitotic clonal expansion and thereby progression of terminal differentiation. Essential for female reproduction because of a critical role in ovarian follicle development. Restricts osteoclastogenesis: together with NFE2L1; represses expression of DSPP during odontoblast differentiation; [Isoform 2]: Essential for gene expression induction in activated macrophages. Plays a major role in immune responses such as CD4(+) T-cell response, granuloma formation and endotoxin shock. Not essential for intracellular bacteria killing; [Isoform 3]: Acts as a dominant negative through heterodimerization with isoform 2. Promotes osteoblast differentiation and osteoclastogenesis.
• Tissue Specificity: Expressed at low levels in the lung, kidney and spleen.
• KEGG Pathway:
  Efferocytosis (hsa04148)
  IL-17 sig.ling pathway (hsa04657)
  TNF sig.ling pathway (hsa04668)
  Tuberculosis (hsa05152)
  Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway:
  ATF4 activates genes in response to endoplasmic reticulum stress (R-HSA-380994)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  Transcriptional Regulation by VENTX (R-HSA-8853884)
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Response of EIF2AK4 (GCN2) to amino acid deficiency (R-HSA-9633012)
  Response of EIF2AK1 (HRI) to heme deficiency (R-HSA-9648895)
  Nuclear events stimulated by ALK signaling in cancer (R-HSA-9725371)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tocopherol	DMBIJZ6	Phase 2	CCAAT/enhancer-binding protein beta (CEBPB) increases the response to substance of Tocopherol.	[62]
Pyrrolidine dithiocarbamate	DM5ZAS6	Investigative	CCAAT/enhancer-binding protein beta (CEBPB) increases the response to substance of Pyrrolidine dithiocarbamate.	[62]

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 CCAAT/enhancer-binding protein beta (CEBPB).	[1]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of CCAAT/enhancer-binding protein beta (CEBPB).	[43]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of CCAAT/enhancer-binding protein beta (CEBPB).	[46]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the phosphorylation of CCAAT/enhancer-binding protein beta (CEBPB).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[16]
Marinol	DM70IK5	Approved	Marinol increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[18]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[20]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[21]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[22]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[10]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[23]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[24]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[25]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[26]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[27]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[28]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[29]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[30]
Lindane	DMB8CNL	Approved	Lindane increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[30]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone affects the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[31]
Imatinib	DM7RJXL	Approved	Imatinib increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[32]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[4]
Deoxycholic acid	DM3GYAL	Approved	Deoxycholic acid increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[33]
Racecadotril	DMFOTZ7	Approved	Racecadotril increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[34]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[35]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[36]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[20]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[3]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[37]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[24]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[38]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[39]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[41]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[42]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[44]
BETULINIC ACID	DMBUI2A	Phase 1	BETULINIC ACID decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[37]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[45]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[48]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[49]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[50]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[51]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[52]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[30]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[53]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[54]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[55]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[56]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[58]
L-Serine	DM6WPIS	Investigative	L-Serine decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[59]
HONOKIOL	DMJWT3X	Investigative	HONOKIOL decreases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[60]
SC-560	DMT1GJL	Investigative	SC-560 increases the expression of CCAAT/enhancer-binding protein beta (CEBPB).	[61]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin affects the binding of CCAAT/enhancer-binding protein beta (CEBPB).	[9]

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