Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCYBO6X)

• DOT Name: Transcription factor Jun (JUN)
• Synonyms: Activator protein 1; AP1; Proto-oncogene c-Jun; Transcription factor AP-1 subunit Jun; V-jun avian sarcoma virus 17 oncogene homolog; p39
• Gene Name: JUN
• UniProt ID: JUN_HUMAN
• PDB ID: 1A02; 1FOS; 1JNM; 1JUN; 1S9K; 1T2K; 5FV8; 5T01; 6Y3V
• Pfam ID: PF00170 ; PF03957
• Sequence:
  MTAKMETTFYDDALNASFLPSESGPYGYSNPKILKQSMTLNLADPVGSLKPHLRAKNSDL
  LTSPDVGLLKLASPELERLIIQSSNGHITTTPTPTQFLCPKNVTDEQEGFAEGFVRALAE
  LHSQNTLPSVTSAAQPVNGAGMVAPAVASVAGGSGSGGFSASLHSEPPVYANLSNFNPGA
  LSSGGGAPSYGAAGLAFPAQPQQQQQPPHHLPQQMPVQHPRLQALKEEPQTVPEMPGETP
  PLSPIDMESQERIKAERKRMRNRIAASKCRKRKLERIARLEEKVKTLKAQNSELASTANM
  LREQVAQLKQKVMNHVNSGCQLMLTQQLQTF
• Function: Transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3'. Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to the AP-1 consensus sequence 5'-TGA[GC]TCA-3' and enhancing its transcriptional activity. Together with FOSB, 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. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells. Binds to the USP28 promoter in colorectal cancer (CRC) cells ; (Microbial infection) Upon Epstein-Barr virus (EBV) infection, binds to viral BZLF1 Z promoter and activates viral BZLF1 expression.
• Tissue Specificity: Expressed in the developing and adult prostate and prostate cancer cells.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  MAPK sig.ling pathway (hsa04010)
  ErbB sig.ling pathway (hsa04012)
  cAMP sig.ling pathway (hsa04024)
  Mitophagy - animal (hsa04137)
  Apoptosis (hsa04210)
  Wnt sig.ling pathway (hsa04310)
  Osteoclast differentiation (hsa04380)
  Focal adhesion (hsa04510)
  Tight junction (hsa04530)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  C-type lectin receptor sig.ling pathway (hsa04625)
  IL-17 sig.ling pathway (hsa04657)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  T cell receptor sig.ling pathway (hsa04660)
  B cell receptor sig.ling pathway (hsa04662)
  TNF sig.ling pathway (hsa04668)
  Neurotrophin sig.ling pathway (hsa04722)
  GnRH sig.ling pathway (hsa04912)
  Estrogen sig.ling pathway (hsa04915)
  Oxytocin sig.ling pathway (hsa04921)
  Relaxin sig.ling pathway (hsa04926)
  Non-alcoholic fatty liver disease (hsa04932)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Epithelial cell sig.ling in Helicobacter pylori infection (hsa05120)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Yersinia infection (hsa05135)
  Leishmaniasis (hsa05140)
  Chagas disease (hsa05142)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coro.virus disease - COVID-19 (hsa05171)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Colorectal cancer (hsa05210)
  Re.l cell carcinoma (hsa05211)
  Breast cancer (hsa05224)
  Choline metabolism in cancer (hsa05231)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Inflammatory bowel disease (hsa05321)
  Rheumatoid arthritis (hsa05323)
  Lipid and atherosclerosis (hsa05417)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  FCERI mediated MAPK activation (R-HSA-2871796)
  Activation of the AP-1 family of transcription factors (R-HSA-450341)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)
  MAPK6/MAPK4 signaling (R-HSA-5687128)
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models (R-HSA-8862803)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Estrogen-dependent gene expression (R-HSA-9018519)
  WNT5 (R-HSA-9673324)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Morphine	DMRMS0L	Approved	Transcription factor Jun (JUN) increases the Hyperpathia ADR of Morphine.	[94]
Fructose	DM43AN2	Approved	Transcription factor Jun (JUN) increases the Metabolism and nutrition disorders ADR of Fructose.	[94]
Chloroxine	DMFZBMQ	Approved	Transcription factor Jun (JUN) increases the Apoptosis ADR of Chloroxine.	[94]
TAM-67	DM26SE7	Investigative	Transcription factor Jun (JUN) increases the Gene mutation ADR of TAM-67.	[94]

78 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 Transcription factor Jun (JUN).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor Jun (JUN).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor Jun (JUN).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor Jun (JUN).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transcription factor Jun (JUN).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription factor Jun (JUN).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor Jun (JUN).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcription factor Jun (JUN).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Transcription factor Jun (JUN).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transcription factor Jun (JUN).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor Jun (JUN).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Transcription factor Jun (JUN).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transcription factor Jun (JUN).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Transcription factor Jun (JUN).	[14]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription factor Jun (JUN).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transcription factor Jun (JUN).	[17]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transcription factor Jun (JUN).	[18]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transcription factor Jun (JUN).	[19]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Transcription factor Jun (JUN).	[20]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Transcription factor Jun (JUN).	[21]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transcription factor Jun (JUN).	[22]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Transcription factor Jun (JUN).	[23]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Transcription factor Jun (JUN).	[24]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Transcription factor Jun (JUN).	[11]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Transcription factor Jun (JUN).	[27]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Transcription factor Jun (JUN).	[29]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Transcription factor Jun (JUN).	[30]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Transcription factor Jun (JUN).	[31]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Transcription factor Jun (JUN).	[32]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Transcription factor Jun (JUN).	[15]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Transcription factor Jun (JUN).	[33]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Transcription factor Jun (JUN).	[34]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Transcription factor Jun (JUN).	[35]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Transcription factor Jun (JUN).	[36]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Transcription factor Jun (JUN).	[37]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Transcription factor Jun (JUN).	[40]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone increases the expression of Transcription factor Jun (JUN).	[41]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of Transcription factor Jun (JUN).	[43]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the activity of Transcription factor Jun (JUN).	[44]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Transcription factor Jun (JUN).	[45]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Transcription factor Jun (JUN).	[46]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the expression of Transcription factor Jun (JUN).	[48]
Fluoxetine	DM3PD2C	Approved	Fluoxetine decreases the expression of Transcription factor Jun (JUN).	[49]
Sertraline	DM0FB1J	Approved	Sertraline increases the expression of Transcription factor Jun (JUN).	[50]
Ritonavir	DMU764S	Approved	Ritonavir increases the expression of Transcription factor Jun (JUN).	[51]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Transcription factor Jun (JUN).	[52]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol increases the expression of Transcription factor Jun (JUN).	[54]
Nilotinib	DM7HXWT	Approved	Nilotinib increases the expression of Transcription factor Jun (JUN).	[57]
Prasterone	DM67VKL	Approved	Prasterone increases the expression of Transcription factor Jun (JUN).	[58]
Masoprocol	DMMVNZ0	Approved	Masoprocol decreases the expression of Transcription factor Jun (JUN).	[59]
Amphetamine	DMSZQAK	Approved	Amphetamine increases the expression of Transcription factor Jun (JUN).	[37]
Mechlorethamine	DM0CVXA	Approved	Mechlorethamine increases the expression of Transcription factor Jun (JUN).	[62]
Fotemustine	DMV62ED	Approved	Fotemustine increases the expression of Transcription factor Jun (JUN).	[39]
Selegiline	DM6034S	Approved	Selegiline increases the expression of Transcription factor Jun (JUN).	[64]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription factor Jun (JUN).	[65]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Transcription factor Jun (JUN).	[66]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transcription factor Jun (JUN).	[67]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Transcription factor Jun (JUN).	[68]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Transcription factor Jun (JUN).	[69]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Transcription factor Jun (JUN).	[70]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of Transcription factor Jun (JUN).	[5]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Transcription factor Jun (JUN).	[71]
I3C	DMIGFOR	Phase 3	I3C increases the expression of Transcription factor Jun (JUN).	[72]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Transcription factor Jun (JUN).	[73]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Transcription factor Jun (JUN).	[74]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Transcription factor Jun (JUN).	[75]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Transcription factor Jun (JUN).	[76]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Transcription factor Jun (JUN).	[77]
Delphinidin	DMS2WIN	Phase 2	Delphinidin increases the expression of Transcription factor Jun (JUN).	[79]
Antroquinonol	DMRGQVZ	Phase 2	Antroquinonol decreases the expression of Transcription factor Jun (JUN).	[81]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor Jun (JUN).	[83]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Transcription factor Jun (JUN).	[84]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Transcription factor Jun (JUN).	[88]
AN-9	DMGL0Q2	Discontinued in Phase 2	AN-9 decreases the expression of Transcription factor Jun (JUN).	[89]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Transcription factor Jun (JUN).	[90]
Taxifolin	DMQJSF9	Preclinical	Taxifolin decreases the expression of Transcription factor Jun (JUN).	[91]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor Jun (JUN).	[92]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor Jun (JUN).	[93]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate increases the phosphorylation of Transcription factor Jun (JUN).	[16]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the phosphorylation of Transcription factor Jun (JUN).	[25]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the phosphorylation of Transcription factor Jun (JUN).	[26]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the phosphorylation of Transcription factor Jun (JUN).	[28]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the phosphorylation of Transcription factor Jun (JUN).	[5]
Topotecan	DMP6G8T	Approved	Topotecan increases the phosphorylation of Transcription factor Jun (JUN).	[39]
Vinblastine	DM5TVS3	Approved	Vinblastine increases the phosphorylation of Transcription factor Jun (JUN).	[42]
Lindane	DMB8CNL	Approved	Lindane increases the phosphorylation of Transcription factor Jun (JUN).	[47]
Colchicine	DM2POTE	Approved	Colchicine increases the phosphorylation of Transcription factor Jun (JUN).	[42]
Docetaxel	DMDI269	Approved	Docetaxel increases the phosphorylation of Transcription factor Jun (JUN).	[53]
Dopamine	DMPGUCF	Approved	Dopamine increases the phosphorylation of Transcription factor Jun (JUN).	[55]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the phosphorylation of Transcription factor Jun (JUN).	[56]
Efavirenz	DMC0GSJ	Approved	Efavirenz increases the phosphorylation of Transcription factor Jun (JUN).	[60]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine increases the phosphorylation of Transcription factor Jun (JUN).	[61]
Sorbitol	DMAN0DE	Approved	Sorbitol increases the phosphorylation of Transcription factor Jun (JUN).	[63]
NCX-4016	DMOX1CU	Phase 2	NCX-4016 increases the phosphorylation of Transcription factor Jun (JUN).	[80]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor Jun (JUN).	[82]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Transcription factor Jun (JUN).	[85]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine decreases the phosphorylation of Transcription factor Jun (JUN).	[86]
Adaphostin	DM16QSG	Phase 1	Adaphostin increases the phosphorylation of Transcription factor Jun (JUN).	[87]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Simvastatin	DM30SGU	Approved	Simvastatin decreases the localization of Transcription factor Jun (JUN).	[38]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN affects the binding of Transcription factor Jun (JUN).	[78]

References

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