Target Information

Target General Infomation
Target ID
T29130
Former ID
TTDS00275
Target Name
Signal transducer and activator of transcription 3
Gene Name
STAT3
Synonyms
Stat3; Transcription factor STAT3; STAT3
Target Type
Successful
Disease Hepatocellular carcinoma [ICD9: 155; ICD10: C22.0]
Multiple myeloma [ICD9: 203; ICD10: C90]
Psoriasis [ICD9: 696; ICD10: L40]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF and other growth factors. 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. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G (By similarity).
BioChemical Class
Transcription factor
Target Validation
T29130
UniProt ID
P40763
Sequence
MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNL
LGEIDQQYSRFLQESNVLYQHNLRRIKQFLQSRYLEKPMEIARIVARCLWEESRLLQTAA
TAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLK
SQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEEL
ADWKRRQQIACIGGPPNICLDRLENWITSLAESQLQTRQQIKKLEELQQKVSYKGDPIVQ
HRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNY
QLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGN
GGRANCDASLIVTEELHLITFETEVYHQGLKIDLETHSLPVVVISNICQMPNAWASILWY
NMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYS
GCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILST
KPPGTFLLRFSESSKEGGVTFTWVEKDISGKTQIQSVEPYTKQQLNNMSFAEIIMGYKIM
DATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPTTCSN
TIDLPMSPRTLDSLMQFGNNGEGAEPSAGGQFESLTFDMELTSECATSPM
Drugs and Mode of Action
Drug(s) Acitretin Drug Info Approved Psoriasis [536361], [542586]
Atiprimod Drug Info Phase 1/2 Multiple myeloma [537114]
OPB-31121 Drug Info Phase 1/2 Hepatocellular carcinoma [523569]
OPB-51602 Drug Info Phase 1 Solid tumours [524640]
Inhibitor Acitretin Drug Info [536235]
Atiprimod Drug Info [537114]
GNF-PF-1399 Drug Info [531262]
OPB-31121 Drug Info [532231]
OPB-51602 Drug Info [533115]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Chemokine signaling pathway
HIF-1 signaling pathway
FoxO signaling pathway
Signaling pathways regulating pluripotency of stem cells
Jak-STAT signaling pathway
Prolactin signaling pathway
Adipocytokine signaling pathway
Toxoplasmosis
Hepatitis C
Hepatitis B
Measles
Epstein-Barr virus infection
Pathways in cancer
Viral carcinogenesis
Proteoglycans in cancer
MicroRNAs in cancer
Pancreatic cancer
Acute myeloid leukemia
Inflammatory bowel disease (IBD)
PANTHER Pathway Angiogenesis
EGF receptor signaling pathway
Inflammation mediated by chemokine and cytokine signaling pathway
Interleukin signaling pathway
JAK/STAT signaling pathway
PDGF signaling pathway
Ras Pathway
CCKR signaling map ST
Pathway Interaction Database GMCSF-mediated signaling events
IL27-mediated signaling events
Signaling events mediated by PTP1B
IL12-mediated signaling events
Signaling events mediated by TCPTP
Signaling events mediated by HDAC Class I
IL2-mediated signaling events
CXCR4-mediated signaling events
EGF receptor (ErbB1) signaling pathway
IFN-gamma pathway
ErbB1 downstream signaling
ErbB2/ErbB3 signaling events
IL6-mediated signaling events
PDGFR-beta signaling pathway
Neurotrophic factor-mediated Trk receptor signaling
IL23-mediated signaling events
Signaling events mediated by Stem cell factor receptor (c-Kit)
FGF signaling pathway
RAC1 signaling pathway
Notch-mediated HES/HEY network
IL12 signaling mediated by STAT4
Reactome Interleukin-6 signaling
Senescence-Associated Secretory Phenotype (SASP)
POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
Transcriptional regulation of pluripotent stem cells
Growth hormone receptor signaling
WikiPathways Serotonin Receptor 2 and STAT3 Signaling
Notch Signaling Pathway
Interferon type I signaling pathways
EPO Receptor Signaling
TGF Beta Signaling Pathway
IL-2 Signaling Pathway
EGF/EGFR Signaling Pathway
IL-4 Signaling Pathway
IL-6 signaling pathway
Signaling of Hepatocyte Growth Factor Receptor
Kit receptor signaling pathway
Nuclear Receptors Meta-Pathway
Estrogen Receptor Pathway
TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
IL-3 Signaling Pathway
Dopaminergic Neurogenesis
Transcriptional regulation of pluripotent stem cells
Mammary gland development pathway - Involution (Stage 4 of 4)
Signaling by SCF-KIT
Interleukin-6 signaling
Growth hormone receptor signaling
JAK/STAT
PDGF Pathway
BDNF signaling pathway
Oncostatin M Signaling Pathway
Adipogenesis
Interleukin-11 Signaling Pathway
AGE/RAGE pathway
Prostate Cancer
TSLP Signaling Pathway
IL-9 Signaling Pathway
IL17 signaling pathway
IL-7 Signaling Pathway
Regulation of Microtubule Cytoskeleton
Leptin signaling pathway
TSH signaling pathway
Cell Differentiation - Index
Cell Differentiation - meta
Signaling by PDGF
NGF signalling via TRKA from the plasma membrane
TFs Regulate miRNAs related to cardiac hypertrophy
MicroRNAs in cardiomyocyte hypertrophy
Physiological and Pathological Hypertrophy of the Heart
Androgen receptor signaling pathway
IL-5 Signaling Pathway
References
Ref 523569ClinicalTrials.gov (NCT01406574) Phase I/II Study of OPB-31121 in Patients With Progressive Hepatocellular Carcinoma. U.S. National Institutes of Health.
Ref 524640ClinicalTrials.gov (NCT02058017) OPB-51602 in Locally Advanced Nasopharyngeal Carcinoma Prior to Definitive Chemoradiotherapy. U.S. National Institutes of Health.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
Ref 542586(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7598).
Ref 531262Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2).
Ref 532231OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells. Cancer Lett. 2013 Jul 10;335(1):145-52.
Ref 533115Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies. Ann Oncol. 2015 May;26(5):998-1005.
Ref 536235Effects of acitretin on the expression of signaling pathway-related genes in epidermal squamous-cell carcinoma cells. Zhonghua Zhong Liu Za Zhi. 2006 Jan;28(1):21-4.
Ref 537114Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.

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