Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTH8FZW)

• DTT Name: Signal transducer and activator of transcription 3 (STAT3)
• Synonyms: Acute-phase response factor; APRF
• Gene Name: STAT3
• DTT Type: Successful target; [1]
• BioChemical Class: Transcription factor
• UniProt ID: STAT3_HUMAN
• TTD ID: T29130
• Sequence:
  MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNL
  LGEIDQQYSRFLQESNVLYQHNLRRIKQFLQSRYLEKPMEIARIVARCLWEESRLLQTAA
  TAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLK
  SQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEEL
  ADWKRRQQIACIGGPPNICLDRLENWITSLAESQLQTRQQIKKLEELQQKVSYKGDPIVQ
  HRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNY
  QLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGN
  GGRANCDASLIVTEELHLITFETEVYHQGLKIDLETHSLPVVVISNICQMPNAWASILWY
  NMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYS
  GCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILST
  KPPGTFLLRFSESSKEGGVTFTWVEKDISGKTQIQSVEPYTKQQLNNMSFAEIIMGYKIM
  DATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPTTCSN
  TIDLPMSPRTLDSLMQFGNNGEGAEPSAGGQFESLTFDMELTSECATSPM
• 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).
• 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

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acitretin	DM8BKU9	Psoriasis vulgaris	EA90	Approved	[1]

13 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Napabucasin	DMDZ6Q3	Colorectal cancer	2B91.Z	Phase 3	[2]
Golotimod	DMKZN3A	Immune System disease	4A01-4B41	Phase 2	[3]
Atiprimod	DM84YEC	Multiple myeloma	2A83	Phase 1/2	[4]
GLG-801	DMY1CP9	Chronic lymphocytic leukaemia	2A82.0	Phase 1/2	[2]
IMX-110	DMNHZS4	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
NT219	DMOYS1N	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[5]
OPB-31121	DM6VGO3	Hepatocellular carcinoma	2C12.02	Phase 1/2	[6]
WP-1066	DMUGHWR	Recurrent glioblastoma	2A00.00	Phase 1/2	[2]
DSP-0337	DM4ZCY0	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
OPB-111077	DM7YFW5	Haematological malignancy	2B33.Y	Phase 1	[8]
OPB-51602	DM760FA	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
TAK-114	DMTXE19	Ulcerative colitis	DD71	Phase 1	[10]
WP1220	DM8RNSB	Cutaneous T-cell lymphoma	2B01	Phase 1	[11]

50 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin analog 1	DM4765M	N. A.	N. A.	Patented	[12]
Curcumin analog 2	DMZ8S6X	N. A.	N. A.	Patented	[12]
Flavonoid derivative 1	DMCQP0B	N. A.	N. A.	Patented	[12]
Flavonoid derivative 2	DMWZARV	N. A.	N. A.	Patented	[12]
Flavonoid derivative 3	DMT7ZEL	N. A.	N. A.	Patented	[12]
Flavonoid derivative 4	DMMOSVD	N. A.	N. A.	Patented	[12]
Flavonoid derivative 5	DMTWAJX	N. A.	N. A.	Patented	[12]
Gold-complexed thiosaccharide derivative 1	DMT1EH9	N. A.	N. A.	Patented	[12]
Gold-complexed thiosaccharide derivative 2	DM9U4OZ	N. A.	N. A.	Patented	[12]
Gold-complexed thiosaccharide derivative 3	DMMOGL8	N. A.	N. A.	Patented	[12]
Oxazole derivative 1	DM7Y2RL	N. A.	N. A.	Patented	[12]
Peptide analog 7	DMKYOLV	N. A.	N. A.	Patented	[12]
Peptidomimetic analog 1	DMMP9N7	N. A.	N. A.	Patented	[12]
Peptidomimetic analog 2	DMN2VZW	N. A.	N. A.	Patented	[12]
Peptidomimetic analog 3	DMPWS9N	N. A.	N. A.	Patented	[12]
Peptidomimetic analog 4	DM9Q0JS	N. A.	N. A.	Patented	[12]
Peptidomimetic analog 5	DMF0DE2	N. A.	N. A.	Patented	[12]
Platinum IV complexe 1	DM8OYI4	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-10	DMP8RQ4	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-11	DMWMZE4	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-12	DMTSQXE	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-13	DMBUZHO	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-20	DMF9J0Y	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-21	DMLMQD4	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-22	DM43Z1G	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-42	DM2E6M7	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-44	DMOJ52P	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-50	DML5I9K	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-51	DMV6GIC	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-52	DMSZWAM	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-53	DMS6EDU	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-54	DMY8FZA	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-Figure16	DMNEGA0	N. A.	N. A.	Patented	[12]
PMID26394986-Compound-Figure17	DMEGBHP	N. A.	N. A.	Patented	[12]
Pyrazole derivative 62	DMN53R0	N. A.	N. A.	Patented	[12]
Pyrazole derivative 63	DMTVAJ0	N. A.	N. A.	Patented	[12]
Pyrazole derivative 64	DMXAURE	N. A.	N. A.	Patented	[12]
Pyrazole derivative 65	DMYTLRJ	N. A.	N. A.	Patented	[12]
Pyrazole derivative 66	DMBYWJI	N. A.	N. A.	Patented	[12]
Quinoline carboxamide derivative 1	DMW5YJB	N. A.	N. A.	Patented	[12]
Quinoline carboxamide derivative 2	DM9XQBG	N. A.	N. A.	Patented	[12]
Quinoline carboxamide derivative 3	DMCAS85	N. A.	N. A.	Patented	[12]
Salicylic acid derivative 1	DMB79QJ	N. A.	N. A.	Patented	[12]
Salicylic acid derivative 2	DMD8C9S	N. A.	N. A.	Patented	[12]
Salicylic acid derivative 3	DM4OGKH	N. A.	N. A.	Patented	[12]
Salicylic acid derivative 4	DM4MAHK	N. A.	N. A.	Patented	[12]
Salicylic acid derivative 5	DM3OZ0F	N. A.	N. A.	Patented	[12]
Salicylic acid derivative 6	DMLBEPW	N. A.	N. A.	Patented	[12]
Salicylic acid derivative 7	DMJFHVN	N. A.	N. A.	Patented	[12]
Tri-substituted purine derivative 1	DM7NTO9	N. A.	N. A.	Patented	[12]

1 #N/A Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
#N/A	DM1HIEZ	N. A.	N. A.	#N/A	[12]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GNF-PF-1399	DM183RV	Discovery agent	N.A.	Investigative	[13]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Liver cancer	2C82	Liver tissue	6.50E-03	-0.12	-0.21
Multiple myeloma	2C82	Bone marrow	6.12E-01	0.14	0.69
Psoriasis	EA90	Skin	1.65E-06	0.17	0.45

References

• [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.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] National Cancer Institute Drug Dictionary (drug id 617379).
• [4] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [5] Clinical pipeline report, company report or official report of Purple Biotech.
• [6] 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.
• [7] Napabucasin, a novel STAT3 inhibitor suppresses proliferation, invasion and stemness of glioblastoma cells. J Exp Clin Cancer Res. 2019 Jul 5;38(1):289.
• [8] 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.
• [9] 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.
• [10] Clinical pipeline report, company report or official report of Gastroenterology.
• [11] Clinical pipeline report, company report or official report of Moleculin Biotech.
• [12] A STAT inhibitor patent review: progress since 2011.Expert Opin Ther Pat. 2015;25(12):1397-421.
• [13] 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.