Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTN3GBV)

• DTT Name: Transcription factor AP-1 (JUN)
• Synonyms: V-jun avian sarcoma virus 17 oncogene homolog; Proto-oncogene c-jun; P39; C-jun proto-oncogene; Activator protein-1; Activator protein 1; AP1; AP-1 transcription factor
• Gene Name: JUN
• DTT Type: Discontinued target; [1]
• Related Disease: Rheumatoid arthritis [ICD-11: FA20]
• BioChemical Class: Basic leucine zipper bZIP
• UniProt ID: JUN_HUMAN
• TTD ID: T69085
• Sequence:
  MTAKMETTFYDDALNASFLPSESGPYGYSNPKILKQSMTLNLADPVGSLKPHLRAKNSDL
  LTSPDVGLLKLASPELERLIIQSSNGHITTTPTPTQFLCPKNVTDEQEGFAEGFVRALAE
  LHSQNTLPSVTSAAQPVNGAGMVAPAVASVAGGSGSGGFSASLHSEPPVYANLSNFNPGA
  LSSGGGAPSYGAAGLAFPAQPQQQQQPPHHLPQQMPVQHPRLQALKEEPQTVPEMPGETP
  PLSPIDMESQERIKAERKRMRNRIAASKCRKRKLERIARLEEKVKTLKAQNSELASTANM
  LREQVAQLKQKVMNHVNSGCQLMLTQQLQTF
• Function: 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. Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  ErbB signaling pathway (hsa04012)
  cAMP signaling pathway (hsa04024)
  Wnt signaling pathway (hsa04310)
  Osteoclast differentiation (hsa04380)
  Focal adhesion (hsa04510)
  Toll-like receptor signaling pathway (hsa04620)
  T cell receptor signaling pathway (hsa04660)
  B cell receptor signaling pathway (hsa04662)
  TNF signaling pathway (hsa04668)
  Neurotrophin signaling pathway (hsa04722)
  GnRH signaling pathway (hsa04912)
  Estrogen signaling pathway (hsa04915)
  Oxytocin signaling pathway (hsa04921)
  Non-alcoholic fatty liver disease (NAFLD) (hsa04932)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Leishmaniasis (hsa05140)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Hepatitis B (hsa05161)
  Influenza A (hsa05164)
  HTLV-I infection (hsa05166)
  Herpes simplex infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Colorectal cancer (hsa05210)
  Renal cell carcinoma (hsa05211)
  Choline metabolism in cancer (hsa05231)
  Inflammatory bowel disease (IBD) (hsa05321)
  Rheumatoid arthritis (hsa05323)
• 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)
  MAPK6/MAPK4 signaling (R-HSA-5687128)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
T-5224	DMD3CUJ	Rheumatoid arthritis	FA20	Discontinued in Phase 2	[1]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PNRI-299	DMDBZGP	Discovery agent	N.A.	Investigative	[2]
TAM-67	DM26SE7	Discovery agent	N.A.	Investigative	[3]
TWS-119	DMS29M4	Discovery agent	N.A.	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	1.13E-03	0.92	1.87

References

• [1] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [2] Chemogenomic identification of Ref-1/AP-1 as a therapeutic target for asthma. Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1169-73.
• [3] AP-1 blockade inhibits the growth of normal and malignant breast cells. Oncogene. 2001 May 17;20(22):2771-80.
• [4] Diversity-oriented synthesis: exploring the intersections between chemistry and biology. Nat Chem Biol. 2005 Jul;1(2):74-84.