Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW6C05J)

• DOT Name: Protein FosB (FOSB)
• Synonyms: FosB proto-oncogene, AP-1 transcription factor subunit; G0/G1 switch regulatory protein 3; Transcription factor AP-1 subunit FosB
• Gene Name: FOSB
• Related Disease:
  Carcinoma
  Cognitive impairment
  Epilepsy
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Asthma
  Atopic dermatitis
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Glioma
  Impulse control disorder
  Intermittent explosive disorder
  Juvenile idiopathic arthritis
  Lung neoplasm
  Movement disorder
  Neoplasm
  Non-small-cell lung cancer
  Osteoarthritis
  Osteosarcoma
  Pneumonia
  Pneumonitis
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Urinary bladder neoplasm
  Anaplastic large cell lymphoma
  Lung carcinoma
  Mood disorder
  Liver cancer
  Lung cancer
  Acute myelogenous leukaemia
  Breast neoplasm
  Cocaine addiction
  Glioblastoma multiforme
  Lymphoma
  Melanoma
  Neuroblastoma
  Pancreatic cancer
• UniProt ID: FOSB_HUMAN
• PDB ID: 5VPA; 5VPB; 5VPC; 5VPD; 5VPE; 5VPF; 6UCI; 6UCL; 6UCM; 7UCC; 7UCD
• Pfam ID: PF00170
• Sequence:
  MFQAFPGDYDSGSRCSSSPSAESQYLSSVDSFGSPPTAAASQECAGLGEMPGSFVPTVTA
  ITTSQDLQWLVQPTLISSMAQSQGQPLASQPPVVDPYDMPGTSYSTPGMSGYSSGGASGS
  GGPSTSGTTSGPGPARPARARPRRPREETLTPEEEEKRRVRRERNKLAAAKCRNRRRELT
  DRLQAETDQLEEEKAELESEIAELQKEKERLEFVLVAHKPGCKIPYEEGPGPGPLAEVRD
  LPGSAPAKEDGFSWLLPPPPPPPLPFQTSQDAPPNLTASLFTHSEVQVLGDPFPVVNPSY
  TSSFVLTCPEVSAFAGAQRTSGSDQPSDPLNSPSLLAL
• Function: Heterodimerizes with proteins of the JUN family to form an AP-1 transcription factor complex, thereby enhancing their DNA binding activity to gene promoters containing an AP-1 consensus sequence 5'-TGA[GC]TCA-3' and enhancing their transcriptional activity. As part of the AP-1 complex, facilitates enhancer selection together with cell-type-specific transcription factors by collaboratively binding to nucleosomal enhancers and recruiting the SWI/SNF (BAF) chromatin remodeling complex to establish accessible chromatin. Together with JUN, plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L, and inducing its transcription in response to activation of the TCR/CD3 signaling pathway. Exhibits transactivation activity in vitro. Involved in the display of nurturing behavior towards newborns. May play a role in neurogenesis in the hippocampus and in learning and memory-related tasks by regulating the expression of various genes involved in neurogenesis, depression and epilepsy. Implicated in behavioral responses related to morphine reward and spatial memory; [Isoform 11]: Exhibits lower transactivation activity than isoform 1 in vitro. The heterodimer with JUN does not display any transcriptional activity, and may thereby act as an transcriptional inhibitor. May be involved in the regulation of neurogenesis in the hippocampus. May play a role in synaptic modifications in nucleus accumbens medium spiny neurons and thereby play a role in adaptive and pathological reward-dependent learning, including maladaptive responses involved in drug addiction. Seems to be more stably expressed with a half-life of ~9.5 hours in cell culture as compared to 1.5 hours half-life of isoform 1.
• Tissue Specificity: .Expressed in the nucleus accumbens of the striatum (at protein level).
• KEGG Pathway:
  Osteoclast differentiation (hsa04380)
  IL-17 sig.ling pathway (hsa04657)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Alcoholism (hsa05034)
• Reactome Pathway:
  NGF-stimulated transcription (R-HSA-9031628)
  Estrogen-dependent gene expression (R-HSA-9018519)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Cognitive impairment	DISH2ERD	Definitive	Biomarker	[2]
Epilepsy	DISBB28L	Definitive	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Strong	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Asthma	DISW9QNS	Strong	Biomarker	[7]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[8]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[11]
Colon cancer	DISVC52G	Strong	Altered Expression	[12]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[14]
Glioma	DIS5RPEH	Strong	Biomarker	[15]
Impulse control disorder	DISRIYJ5	Strong	Biomarker	[16]
Intermittent explosive disorder	DIST148I	Strong	Biomarker	[16]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[17]
Lung neoplasm	DISVARNB	Strong	Biomarker	[18]
Movement disorder	DISOJJ2D	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[22]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[9]
Pneumonia	DIS8EF3M	Strong	Biomarker	[23]
Pneumonitis	DIS88E0K	Strong	Biomarker	[23]
Prostate cancer	DISF190Y	Strong	Altered Expression	[24]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[24]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[25]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[26]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[27]
Anaplastic large cell lymphoma	DISP4D1R	moderate	Altered Expression	[28]
Lung carcinoma	DISTR26C	moderate	Biomarker	[29]
Mood disorder	DISLVMWO	moderate	Biomarker	[30]
Liver cancer	DISDE4BI	Disputed	Biomarker	[31]
Lung cancer	DISCM4YA	Disputed	Biomarker	[18]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[32]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[33]
Cocaine addiction	DISHTRXG	Limited	Biomarker	[34]
Glioblastoma multiforme	DISK8246	Limited	Genetic Variation	[4]
Lymphoma	DISN6V4S	Limited	Altered Expression	[28]
Melanoma	DIS1RRCY	Limited	Altered Expression	[35]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[36]
Pancreatic cancer	DISJC981	Limited	Biomarker	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein FosB (FOSB).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein FosB (FOSB).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein FosB (FOSB).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein FosB (FOSB).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein FosB (FOSB).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein FosB (FOSB).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein FosB (FOSB).	[44]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Protein FosB (FOSB).	[45]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Protein FosB (FOSB).	[46]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Protein FosB (FOSB).	[47]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Protein FosB (FOSB).	[48]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Protein FosB (FOSB).	[49]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Protein FosB (FOSB).	[50]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Protein FosB (FOSB).	[51]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Protein FosB (FOSB).	[52]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Protein FosB (FOSB).	[53]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Protein FosB (FOSB).	[54]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Protein FosB (FOSB).	[55]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Protein FosB (FOSB).	[56]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Protein FosB (FOSB).	[57]
Amphetamine	DMSZQAK	Approved	Amphetamine increases the expression of Protein FosB (FOSB).	[54]
Potassium chloride	DMMTAJC	Approved	Potassium chloride increases the expression of Protein FosB (FOSB).	[45]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein FosB (FOSB).	[58]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Protein FosB (FOSB).	[39]
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the expression of Protein FosB (FOSB).	[59]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein FosB (FOSB).	[60]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Protein FosB (FOSB).	[42]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Protein FosB (FOSB).	[61]
Lithium	DMZ3OU6	Phase 2	Lithium increases the expression of Protein FosB (FOSB).	[62]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein FosB (FOSB).	[64]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein FosB (FOSB).	[65]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 decreases the activity of Protein FosB (FOSB).	[66]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Protein FosB (FOSB).	[67]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein FosB (FOSB).	[68]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein FosB (FOSB).	[69]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate affects the expression of Protein FosB (FOSB).	[70]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Protein FosB (FOSB).	[71]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein FosB (FOSB).	[63]

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