Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHJT3X)

• DTT Name: STAT3 messenger RNA (STAT3 mRNA)
• Synonyms: Transcription factor STAT3 (mRNA); Stat3 (mRNA); Signal transducer and activator of transcription 3 (mRNA); Acute-phase response factor (mRNA); APRF (mRNA)
• Gene Name: STAT3
• DTT Type: Clinical trial target; [1]
• BioChemical Class: mRNA target
• UniProt ID: STAT3_HUMAN
• TTD ID: T86803
• Sequence:
  MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNL
  LGEIDQQYSRFLQESNVLYQHNLRRIKQFLQSRYLEKPMEIARIVARCLWEESRLLQTAA
  TAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLK
  SQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEEL
  ADWKRRQQIACIGGPPNICLDRLENWITSLAESQLQTRQQIKKLEELQQKVSYKGDPIVQ
  HRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNY
  QLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGN
  GGRANCDASLIVTEELHLITFETEVYHQGLKIDLETHSLPVVVISNICQMPNAWASILWY
  NMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYS
  GCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILST
  KPPGTFLLRFSESSKEGGVTFTWVEKDISGKTQIQSVEPYTKQQLNNMSFAEIIMGYKIM
  DATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPTTCSN
  TIDLPMSPRTLDSLMQFGNNGEGAEPSAGGQFESLTFDMELTSECATSPM
• Function: Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity. Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1. Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation. May play an apoptotic role by transctivating BIRC5 expression under LEP activation. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion. Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors.
• KEGG Pathway:
  Chemokine signaling pathway (hsa04062)
  HIF-1 signaling pathway (hsa04066)
  FoxO signaling pathway (hsa04068)
  Signaling pathways regulating pluripotency of stem cells (hsa04550)
  Jak-STAT signaling pathway (hsa04630)
  Prolactin signaling pathway (hsa04917)
  Adipocytokine signaling pathway (hsa04920)
  Toxoplasmosis (hsa05145)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Proteoglycans in cancer (hsa05205)
  MicroRNAs in cancer (hsa05206)
  Pancreatic cancer (hsa05212)
  Acute myeloid leukemia (hsa05221)
  Inflammatory bowel disease (IBD) (hsa05321)
• Reactome Pathway:
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation (R-HSA-2892247)
  Transcriptional regulation of pluripotent stem cells (R-HSA-452723)
  Growth hormone receptor signaling (R-HSA-982772)
  Interleukin-6 signaling (R-HSA-1059683)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS-STAT3	DMDTNFB	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
C188-9	DMOV2ZD	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 113176	DM5QEP4	Discovery agent	N.A.	Investigative	[3]
ISIS 113187	DM4E6Y8	Discovery agent	N.A.	Investigative	[3]
ISIS 113209	DMGVN7A	Discovery agent	N.A.	Investigative	[3]
ISIS 113210	DMZWH6E	Discovery agent	N.A.	Investigative	[3]
ISIS 17148	DMPZ9D3	Discovery agent	N.A.	Investigative	[3]
ISIS 17152	DME7VZG	Discovery agent	N.A.	Investigative	[3]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
• [3] US patent application no. 7,098,192, Antisense oligonucleotide modulation of STAT3 expression.