Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIAC6W4)

• DOT Name: Core-binding factor subunit beta (CBFB)
• Synonyms: CBF-beta; Polyomavirus enhancer-binding protein 2 beta subunit; PEA2-beta; PEBP2-beta; SL3-3 enhancer factor 1 subunit beta; SL3/AKV core-binding factor beta subunit
• Gene Name: CBFB
• Related Disease:
  Adenocarcinoma
  T-cell acute lymphoblastic leukaemia
  Acute myelomonocytic leukemia M4
  Advanced cancer
  Bone development disease
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Chromosomal disorder
  Cleidocranial dysplasia 2
  Epithelial ovarian cancer
  Estrogen-receptor positive breast cancer
  Gastric cancer
  Gastric neoplasm
  Hematologic disease
  Hepatitis B virus infection
  Immunodeficiency
  Isolated cleft palate
  Leukopenia
  Myelodysplastic syndrome
  Myeloid leukaemia
  Neoplasm
  Osteoporosis
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Stomach cancer
  Wilms tumor
  Systemic mastocytosis
  Acute lymphocytic leukaemia
  Acute leukaemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Childhood acute lymphoblastic leukemia
  Colorectal carcinoma
  Colorectal neoplasm
  leukaemia
  Leukemia
  Small lymphocytic lymphoma
• UniProt ID: PEBB_HUMAN
• PDB ID: 1CL3; 1E50; 1H9D; 4N9F; 6NIL; 6P59; 6VGD; 6VGE; 6VGG; 8CX0; 8CX1; 8CX2; 8E40; 8FVI; 8FVJ; 8H0I; 8J62
• Pfam ID: PF02312
• Sequence:
  MPRVVPDQRSKFENEEFFRKLSRECEIKYTGFRDRPHEERQARFQNACRDGRSEIAFVAT
  GTNLSLQFFPASWQGEQRQTPSREYVDLEREAGKVYLKAPMILNGVCVIWKGWIDLQRLD
  GMGCLEFDEERAQQEDALAQQAFEEARRRTREFEDRDRSHREEMEVRVSQLLAVTGKKTT
  RP
• Function: Forms the heterodimeric complex core-binding factor (CBF) with RUNX family proteins (RUNX1, RUNX2, and RUNX3). RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation.
• Reactome Pathway:
  Transcriptional regulation by RUNX2 (R-HSA-8878166)
  RUNX1 regulates estrogen receptor mediated transcription (R-HSA-8931987)
  Regulation of RUNX1 Expression and Activity (R-HSA-8934593)
  RUNX1 regulates expression of components of tight junctions (R-HSA-8935964)
  RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459)
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  RUNX1 regulates transcription of genes involved in differentiation of keratinocytes (R-HSA-8939242)
  RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243)
  RUNX1 regulates transcription of genes involved in BCR signaling (R-HSA-8939245)
  RUNX1 regulates transcription of genes involved in differentiation of myeloid cells (R-HSA-8939246)
  RUNX1 regulates transcription of genes involved in interleukin signaling (R-HSA-8939247)
  RUNX1 regulates transcription of genes involved in WNT signaling (R-HSA-8939256)
  Regulation of RUNX2 expression and activity (R-HSA-8939902)
  RUNX2 regulates osteoblast differentiation (R-HSA-8940973)
  RUNX2 regulates chondrocyte maturation (R-HSA-8941284)
  RUNX2 regulates bone development (R-HSA-8941326)
  RUNX2 regulates genes involved in cell migration (R-HSA-8941332)
  RUNX2 regulates genes involved in differentiation of myeloid cells (R-HSA-8941333)
  Regulation of RUNX3 expression and activity (R-HSA-8941858)
  RUNX3 Regulates Immune Response and Cell Migration (R-HSA-8949275)
  RUNX3 regulates RUNX1-mediated transcription (R-HSA-8951911)
  RUNX3 regulates p14-ARF (R-HSA-8951936)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) (R-HSA-8877330)

Molecular Interaction Atlas (MIA) of This DOT

39 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Genetic Variation	[1]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Biomarker	[2]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Bone development disease	DISVKAZS	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[7]
Cleidocranial dysplasia 2	DISLTJ8W	Strong	Autosomal dominant	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[9]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Genetic Variation	[10]
Gastric cancer	DISXGOUK	Strong	Biomarker	[11]
Gastric neoplasm	DISOKN4Y	Strong	Altered Expression	[11]
Hematologic disease	DIS9XD9A	Strong	Biomarker	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[13]
Immunodeficiency	DIS093I0	Strong	Biomarker	[14]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[5]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[15]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[16]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[18]
Osteoporosis	DISF2JE0	Strong	Biomarker	[19]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[6]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[9]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[9]
Stomach cancer	DISKIJSX	Strong	Biomarker	[11]
Wilms tumor	DISB6T16	Strong	Altered Expression	[20]
Systemic mastocytosis	DISNQ2OY	moderate	Genetic Variation	[21]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Genetic Variation	[22]
Acute leukaemia	DISDQFDI	Limited	Genetic Variation	[23]
Acute monocytic leukemia	DIS28NEL	Limited	Genetic Variation	[24]
Acute myelogenous leukaemia	DISCSPTN	Limited	Unknown	[25]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Genetic Variation	[26]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[27]
Colorectal neoplasm	DISR1UCN	Limited	Altered Expression	[27]
leukaemia	DISS7D1V	Limited	Altered Expression	[28]
Leukemia	DISNAKFL	Limited	Altered Expression	[28]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Core-binding factor subunit beta (CBFB).	[30]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Core-binding factor subunit beta (CBFB).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Core-binding factor subunit beta (CBFB).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Core-binding factor subunit beta (CBFB).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Core-binding factor subunit beta (CBFB).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Core-binding factor subunit beta (CBFB).	[35]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Core-binding factor subunit beta (CBFB).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Core-binding factor subunit beta (CBFB).	[37]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Core-binding factor subunit beta (CBFB).	[39]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Core-binding factor subunit beta (CBFB).	[40]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Core-binding factor subunit beta (CBFB).	[39]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Core-binding factor subunit beta (CBFB).	[41]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Core-binding factor subunit beta (CBFB).	[42]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Core-binding factor subunit beta (CBFB).	[43]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Core-binding factor subunit beta (CBFB).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Core-binding factor subunit beta (CBFB).	[44]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Core-binding factor subunit beta (CBFB).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Core-binding factor subunit beta (CBFB).	[46]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Core-binding factor subunit beta (CBFB).	[48]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Core-binding factor subunit beta (CBFB).	[36]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Core-binding factor subunit beta (CBFB).	[49]

2 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 Core-binding factor subunit beta (CBFB).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Core-binding factor subunit beta (CBFB).	[47]

References

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• [5] Core binding factor beta (CBFB) haploinsufficiency due to an interstitial deletion at 16q21q22 resulting in delayed cranial ossification, cleft palate, congenital heart anomalies, and feeding difficulties but favorable outcome.Am J Med Genet A. 2006 Nov 1;140(21):2349-54. doi: 10.1002/ajmg.a.31479.
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