Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTN7R6K)

• DTT Name: Signal transducer and activator of transcription 1 (STAT1)
• Synonyms: Transcription factor ISGF-3 components p91/p84; Signal transducers and activators of transcription factor; Signal transducer and activator of transcription 1-alpha/beta; STAT-1; P91
• Gene Name: STAT1
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Transcription factor
• UniProt ID: STAT1_HUMAN
• TTD ID: T64205
• Sequence:
  MSQWYELQQLDSKFLEQVHQLYDDSFPMEIRQYLAQWLEKQDWEHAANDVSFATIRFHDL
  LSQLDDQYSRFSLENNFLLQHNIRKSKRNLQDNFQEDPIQMSMIIYSCLKEERKILENAQ
  RFNQAQSGNIQSTVMLDKQKELDSKVRNVKDKVMCIEHEIKSLEDLQDEYDFKCKTLQNR
  EHETNGVAKSDQKQEQLLLKKMYLMLDNKRKEVVHKIIELLNVTELTQNALINDELVEWK
  RRQQSACIGGPPNACLDQLQNWFTIVAESLQQVRQQLKKLEELEQKYTYEHDPITKNKQV
  LWDRTFSLFQQLIQSSFVVERQPCMPTHPQRPLVLKTGVQFTVKLRLLVKLQELNYNLKV
  KVLFDKDVNERNTVKGFRKFNILGTHTKVMNMEESTNGSLAAEFRHLQLKEQKNAGTRTN
  EGPLIVTEELHSLSFETQLCQPGLVIDLETTSLPVVVISNVSQLPSGWASILWYNMLVAE
  PRNLSFFLTPPCARWAQLSEVLSWQFSSVTKRGLNVDQLNMLGEKLLGPNASPDGLIPWT
  RFCKENINDKNFPFWLWIESILELIKKHLLPLWNDGCIMGFISKERERALLKDQQPGTFL
  LRFSESSREGAITFTWVERSQNGGEPDFHAVEPYTKKELSAVTFPDIIRNYKVMAAENIP
  ENPLKYLYPNIDKDHAFGKYYSRPKEAPEPMELDGPKGTGYIKTELISVSEVHPSRLQTT
  DNLLPMSPEEFDEVSRIVGSVEFDSMMNTV
• Function: Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors.
• KEGG Pathway:
  Chemokine signaling pathway (hsa04062)
  Osteoclast differentiation (hsa04380)
  Toll-like receptor signaling pathway (hsa04620)
  Jak-STAT signaling pathway (hsa04630)
  Prolactin signaling pathway (hsa04917)
  Thyroid hormone signaling pathway (hsa04919)
  Leishmaniasis (hsa05140)
  Toxoplasmosis (hsa05145)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Herpes simplex infection (hsa05168)
  Pathways in cancer (hsa05200)
  Pancreatic cancer (hsa05212)
  Inflammatory bowel disease (IBD) (hsa05321)
• Reactome Pathway: ISG15 antiviral mechanism (R-HSA-1169408)

Molecular Interaction Atlas (MIA) of This DTT

5 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Oxazole derivative 1	DM7Y2RL	N. A.	N. A.	Patented	[1]
Peptide analog 8	DMFG7A8	N. A.	N. A.	Patented	[1]
Peptidomimetic analog 5	DMF0DE2	N. A.	N. A.	Patented	[1]
Platinum IV complexe 1	DM8OYI4	N. A.	N. A.	Patented	[1]
PMID26394986-Compound-10	DMP8RQ4	N. A.	N. A.	Patented	[1]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AVT-02 UE	DM8NA4M	Skin infection	1F28-1G0Z	Discontinued in Phase 2	[2]

References

• [1] A STAT inhibitor patent review: progress since 2011.Expert Opin Ther Pat. 2015;25(12):1397-421.
• [2] Avontec Announces Results of a Multiple Dose Clinical Phase I Study with Its Drug Candidate AVT-02 UE Ointment After Topical Treatment in Male Healthy Volunteers. Avontec. 2008.