Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU3QYEF)

• DOT Name: Transcription factor RelB (RELB)
• Synonyms: I-Rel
• Gene Name: RELB
• Related Disease:
  Nephropathy
  Advanced cancer
  Alzheimer disease
  Arthritis
  Atopic dermatitis
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Classic Hodgkin lymphoma
  Coronary atherosclerosis
  Endometrial carcinoma
  Esophageal cancer
  Glioma
  Head and neck cancer
  Head and neck carcinoma
  Hepatocellular carcinoma
  Lupus
  Lymphoma
  Metastatic prostate carcinoma
  Multiple sclerosis
  Myocardial ischemia
  Neoplasm
  Neoplasm of esophagus
  Prediabetes syndrome
  Prostate neoplasm
  Systemic lupus erythematosus
  Uveal Melanoma
  Intracerebral hemorrhage
  Lung adenocarcinoma
  Small lymphocytic lymphoma
  Bladder cancer
  Cystitis
  Glioblastoma multiforme
  Immunodeficiency 53
  Myasthenia gravis
  Primary cutaneous T-cell lymphoma
  Type-1 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Vitamin D-dependent rickets, type 2
  X-linked dominant hypophosphatemic rickets
• UniProt ID: RELB_HUMAN
• Pfam ID: PF16180 ; PF16181 ; PF16179 ; PF00554
• Sequence:
  MLRSGPASGPSVPTGRAMPSRRVARPPAAPELGALGSPDLSSLSLAVSRSTDELEIIDEY
  IKENGFGLDGGQPGPGEGLPRLVSRGAASLSTVTLGPVAPPATPPPWGCPLGRLVSPAPG
  PGPQPHLVITEQPKQRGMRFRYECEGRSAGSILGESSTEASKTLPAIELRDCGGLREVEV
  TACLVWKDWPHRVHPHSLVGKDCTDGICRVRLRPHVSPRHSFNNLGIQCVRKKEIEAAIE
  RKIQLGIDPYNAGSLKNHQEVDMNVVRICFQASYRDQQGQMRRMDPVLSEPVYDKKSTNT
  SELRICRINKESGPCTGGEELYLLCDKVQKEDISVVFSRASWEGRADFSQADVHRQIAIV
  FKTPPYEDLEIVEPVTVNVFLQRLTDGVCSEPLPFTYLPRDHDSYGVDKKRKRGMPDVLG
  ELNSSDPHGIESKRRKKKPAILDHFLPNHGSGPFLPPSALLPDPDFFSGTVSLPGLEPPG
  GPDLLDDGFAYDPTAPTLFTMLDLLPPAPPHASAVVCSGGAGAVVGETPGPEPLTLDSYQ
  APGPGDGGTASLVGSNMFPNHYREAAFGGGLLSPGPEAT
• Function: NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer in a CRY1/CRY2 independent manner. Increased repression of the heterodimer is seen in the presence of NFKB2/p52. Is required for both T and B lymphocyte maturation and function.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  NF-kappa B sig.ling pathway (hsa04064)
  Osteoclast differentiation (hsa04380)
  C-type lectin receptor sig.ling pathway (hsa04625)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Epstein-Barr virus infection (hsa05169)
• Reactome Pathway:
  CD209 (DC-SIGN) signaling (R-HSA-5621575)
  NIK-->noncanonical NF-kB signaling (R-HSA-5676590)
  Dectin-1 mediated noncanonical NF-kB signaling (R-HSA-5607761)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephropathy	DISXWP4P	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[3]
Arthritis	DIST1YEL	Strong	Posttranslational Modification	[4]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[5]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[8]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[6]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[9]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[10]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[8]
Glioma	DIS5RPEH	Strong	Biomarker	[11]
Head and neck cancer	DISBPSQZ	Strong	Altered Expression	[2]
Head and neck carcinoma	DISOU1DS	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Lupus	DISOKJWA	Strong	Biomarker	[13]
Lymphoma	DISN6V4S	Strong	Biomarker	[6]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[14]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[15]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[8]
Prediabetes syndrome	DISH2I53	Strong	Biomarker	[17]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[18]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[13]
Uveal Melanoma	DISA7ZGL	Strong	Altered Expression	[19]
Intracerebral hemorrhage	DISC81BT	moderate	Biomarker	[20]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[21]
Small lymphocytic lymphoma	DIS30POX	moderate	Posttranslational Modification	[22]
Bladder cancer	DISUHNM0	Limited	Biomarker	[23]
Cystitis	DIS2D4B9	Limited	Altered Expression	[23]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[24]
Immunodeficiency 53	DISQ3Q2J	Limited	Autosomal recessive	[25]
Myasthenia gravis	DISELRCI	Limited	Altered Expression	[26]
Primary cutaneous T-cell lymphoma	DIS35WVW	Limited	Biomarker	[27]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[28]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[23]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[23]
Vitamin D-dependent rickets, type 2	DISZHFC3	Limited	Genetic Variation	[28]
X-linked dominant hypophosphatemic rickets	DISU3OP6	Limited	Genetic Variation	[28]

33 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 Transcription factor RelB (RELB).	[29]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcription factor RelB (RELB).	[30]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor RelB (RELB).	[31]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription factor RelB (RELB).	[32]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor RelB (RELB).	[33]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor RelB (RELB).	[30]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Transcription factor RelB (RELB).	[34]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transcription factor RelB (RELB).	[35]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor RelB (RELB).	[36]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Transcription factor RelB (RELB).	[37]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transcription factor RelB (RELB).	[38]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transcription factor RelB (RELB).	[38]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transcription factor RelB (RELB).	[39]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Transcription factor RelB (RELB).	[40]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Transcription factor RelB (RELB).	[41]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transcription factor RelB (RELB).	[37]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Transcription factor RelB (RELB).	[42]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Transcription factor RelB (RELB).	[43]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Transcription factor RelB (RELB).	[44]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Transcription factor RelB (RELB).	[45]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Transcription factor RelB (RELB).	[44]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Transcription factor RelB (RELB).	[46]
Omacetaxine mepesuccinate	DMPU2WX	Approved	Omacetaxine mepesuccinate increases the expression of Transcription factor RelB (RELB).	[47]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Transcription factor RelB (RELB).	[48]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Transcription factor RelB (RELB).	[49]
Abexinostat	DM91LGU	Phase 3	Abexinostat decreases the expression of Transcription factor RelB (RELB).	[50]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Transcription factor RelB (RELB).	[51]
Contigoside B	DMX9V8K	Phase 2/3	Contigoside B increases the expression of Transcription factor RelB (RELB).	[52]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transcription factor RelB (RELB).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transcription factor RelB (RELB).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor RelB (RELB).	[55]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Transcription factor RelB (RELB).	[56]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Transcription factor RelB (RELB).	[57]

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