Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T29130
(Former ID: TTDS00275)
|
|||||
| Target Name |
Signal transducer and activator of transcription 3 (STAT3)
|
|||||
| Synonyms |
Acute-phase response factor; APRF
|
|||||
| Gene Name |
STAT3
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Psoriasis [ICD-11: EA90] | |||||
| Function |
Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. 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 (By similarity). 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 (By similarity).
Click to Show/Hide
|
|||||
| BioChemical Class |
Transcription factor
|
|||||
| UniProt ID | ||||||
| Sequence |
MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNL
LGEIDQQYSRFLQESNVLYQHNLRRIKQFLQSRYLEKPMEIARIVARCLWEESRLLQTAA TAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLK SQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEEL ADWKRRQQIACIGGPPNICLDRLENWITSLAESQLQTRQQIKKLEELQQKVSYKGDPIVQ HRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNY QLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGN GGRANCDASLIVTEELHLITFETEVYHQGLKIDLETHSLPVVVISNICQMPNAWASILWY NMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYS GCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILST KPPGTFLLRFSESSKEGGVTFTWVEKDISGKTQIQSVEPYTKQQLNNMSFAEIIMGYKIM DATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPTTCSN TIDLPMSPRTLDSLMQFGNNGEGAEPSAGGQFESLTFDMELTSECATSPM Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A00142 ; BADD_A02356 ; BADD_A03237 ; BADD_A05675 | |||||
| HIT2.0 ID | T96OOK | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Acitretin | Drug Info | Approved | Psoriasis vulgaris | [2], [3] | |
| Clinical Trial Drug(s) | [+] 13 Clinical Trial Drugs | + | ||||
| 1 | Napabucasin | Drug Info | Phase 3 | Pancreatic cancer | [4] | |
| 2 | Golotimod | Drug Info | Phase 2 | Immune System disease | [5] | |
| 3 | Atiprimod | Drug Info | Phase 1/2 | Multiple myeloma | [6] | |
| 4 | GLG-801 | Drug Info | Phase 1/2 | Chronic lymphocytic leukaemia | [4] | |
| 5 | IMX-110 | Drug Info | Phase 1/2 | Solid tumour/cancer | [4] | |
| 6 | NT219 | Drug Info | Phase 1/2 | Solid tumour/cancer | [7] | |
| 7 | OPB-31121 | Drug Info | Phase 1/2 | Hepatocellular carcinoma | [8] | |
| 8 | WP-1066 | Drug Info | Phase 1/2 | Recurrent glioblastoma | [4] | |
| 9 | DSP-0337 | Drug Info | Phase 1 | Solid tumour/cancer | [9] | |
| 10 | OPB-111077 | Drug Info | Phase 1 | Hepatocellular carcinoma | [10] | |
| 11 | OPB-51602 | Drug Info | Phase 1 | Solid tumour/cancer | [11] | |
| 12 | TAK-114 | Drug Info | Phase 1 | Ulcerative colitis | [12] | |
| 13 | WP1220 | Drug Info | Phase 1 | Cutaneous T-cell lymphoma | [13] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 65 Inhibitor drugs | + | ||||
| 1 | Acitretin | Drug Info | [1] | |||
| 2 | Napabucasin | Drug Info | [4] | |||
| 3 | Golotimod | Drug Info | [14] | |||
| 4 | Atiprimod | Drug Info | [6] | |||
| 5 | GLG-801 | Drug Info | [4] | |||
| 6 | IMX-110 | Drug Info | [4] | |||
| 7 | NT219 | Drug Info | [15] | |||
| 8 | OPB-31121 | Drug Info | [16] | |||
| 9 | WP-1066 | Drug Info | [4], [17] | |||
| 10 | DSP-0337 | Drug Info | [18] | |||
| 11 | OPB-111077 | Drug Info | [19] | |||
| 12 | OPB-51602 | Drug Info | [20] | |||
| 13 | WP1220 | Drug Info | [21] | |||
| 14 | Curcumin analog 1 | Drug Info | [22] | |||
| 15 | Curcumin analog 2 | Drug Info | [22] | |||
| 16 | Flavonoid derivative 1 | Drug Info | [22] | |||
| 17 | Flavonoid derivative 2 | Drug Info | [22] | |||
| 18 | Flavonoid derivative 3 | Drug Info | [22] | |||
| 19 | Flavonoid derivative 4 | Drug Info | [22] | |||
| 20 | Flavonoid derivative 5 | Drug Info | [22] | |||
| 21 | Gold-complexed thiosaccharide derivative 1 | Drug Info | [22] | |||
| 22 | Gold-complexed thiosaccharide derivative 2 | Drug Info | [22] | |||
| 23 | Gold-complexed thiosaccharide derivative 3 | Drug Info | [22] | |||
| 24 | Oxazole derivative 1 | Drug Info | [22] | |||
| 25 | Peptide analog 7 | Drug Info | [22] | |||
| 26 | Peptidomimetic analog 1 | Drug Info | [22] | |||
| 27 | Peptidomimetic analog 2 | Drug Info | [22] | |||
| 28 | Peptidomimetic analog 3 | Drug Info | [22] | |||
| 29 | Peptidomimetic analog 4 | Drug Info | [22] | |||
| 30 | Peptidomimetic analog 5 | Drug Info | [22] | |||
| 31 | Platinum IV complexe 1 | Drug Info | [22] | |||
| 32 | PMID26394986-Compound-10 | Drug Info | [22] | |||
| 33 | PMID26394986-Compound-11 | Drug Info | [22] | |||
| 34 | PMID26394986-Compound-12 | Drug Info | [22] | |||
| 35 | PMID26394986-Compound-13 | Drug Info | [22] | |||
| 36 | PMID26394986-Compound-20 | Drug Info | [22] | |||
| 37 | PMID26394986-Compound-21 | Drug Info | [22] | |||
| 38 | PMID26394986-Compound-22 | Drug Info | [22] | |||
| 39 | PMID26394986-Compound-42 | Drug Info | [22] | |||
| 40 | PMID26394986-Compound-43 | Drug Info | [22] | |||
| 41 | PMID26394986-Compound-44 | Drug Info | [22] | |||
| 42 | PMID26394986-Compound-50 | Drug Info | [22] | |||
| 43 | PMID26394986-Compound-51 | Drug Info | [22] | |||
| 44 | PMID26394986-Compound-52 | Drug Info | [22] | |||
| 45 | PMID26394986-Compound-53 | Drug Info | [22] | |||
| 46 | PMID26394986-Compound-54 | Drug Info | [22] | |||
| 47 | PMID26394986-Compound-Figure16 | Drug Info | [22] | |||
| 48 | PMID26394986-Compound-Figure17 | Drug Info | [22] | |||
| 49 | Pyrazole derivative 62 | Drug Info | [22] | |||
| 50 | Pyrazole derivative 63 | Drug Info | [22] | |||
| 51 | Pyrazole derivative 64 | Drug Info | [22] | |||
| 52 | Pyrazole derivative 65 | Drug Info | [22] | |||
| 53 | Pyrazole derivative 66 | Drug Info | [22] | |||
| 54 | Quinoline carboxamide derivative 1 | Drug Info | [22] | |||
| 55 | Quinoline carboxamide derivative 2 | Drug Info | [22] | |||
| 56 | Quinoline carboxamide derivative 3 | Drug Info | [22] | |||
| 57 | Salicylic acid derivative 1 | Drug Info | [22] | |||
| 58 | Salicylic acid derivative 2 | Drug Info | [22] | |||
| 59 | Salicylic acid derivative 3 | Drug Info | [22] | |||
| 60 | Salicylic acid derivative 4 | Drug Info | [22] | |||
| 61 | Salicylic acid derivative 5 | Drug Info | [22] | |||
| 62 | Salicylic acid derivative 6 | Drug Info | [22] | |||
| 63 | Salicylic acid derivative 7 | Drug Info | [22] | |||
| 64 | Tri-substituted purine derivative 1 | Drug Info | [22] | |||
| 65 | GNF-PF-1399 | Drug Info | [23] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | TAK-114 | Drug Info | [12] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Effects 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 2 | URL: 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 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 5 | ClinicalTrials.gov (NCT00756951) Dose Ranging Study to Assess the Safety and Efficacy of SCV-07 for the Delay to Onset of Severe Oral Mucositis in Patients Receiving Chemoradiation Therapy for Head and Neck Cancer. U.S. National Institutes of Health. | |||||
| REF 6 | Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. | |||||
| REF 7 | ClinicalTrials.gov (NCT04474470) A Study to Evaluate NT219 Alone and in Combination With ERBITUX (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer. U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT01406574) Phase I/II Study of OPB-31121 in Patients With Progressive Hepatocellular Carcinoma. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT03416816) A Study of DSP-0337 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile. U.S. National Institutes of Health. | |||||
| REF 10 | ClinicalTrials.gov (NCT02250170) Safety and Biomarker of OPB-111077 in Subjects With Advanced Solid Tumor. U.S. National Institutes of Health. | |||||
| REF 11 | ClinicalTrials.gov (NCT02058017) OPB-51602 in Locally Advanced Nasopharyngeal Carcinoma Prior to Definitive Chemoradiotherapy. U.S. National Institutes of Health. | |||||
| REF 12 | Clinical pipeline report, company report or official report of Gastroenterology. | |||||
| REF 13 | ClinicalTrials.gov (NCT04702503) Study of WP1220 for the Treatment of Adult Subjects With Cutaneous T-Cell Lymphoma (CTCL). U.S. National Institutes of Health. | |||||
| REF 14 | National Cancer Institute Drug Dictionary (drug id 617379). | |||||
| REF 15 | Clinical pipeline report, company report or official report of Purple Biotech. | |||||
| REF 16 | OPB-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 17 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 18 | Napabucasin, a novel STAT3 inhibitor suppresses proliferation, invasion and stemness of glioblastoma cells. J Exp Clin Cancer Res. 2019 Jul 5;38(1):289. | |||||
| REF 19 | Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma. Cancer Res Treat. 2019 Apr;51(2):510-518. | |||||
| REF 20 | Phase 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 21 | Clinical pipeline report, company report or official report of Moleculin Biotech. | |||||
| REF 22 | A STAT inhibitor patent review: progress since 2011.Expert Opin Ther Pat. 2015;25(12):1397-421. | |||||
| REF 23 | In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.