Id: acc1526
Group: 1sens
Protein: STAT3
Gene Symbol: STAT3
Protein Id: P40763
Protein Name: STAT3_HUMAN
PTM: phosphorylation
Site: Ser727
Site Sequence: CSNTIDLPMSPRTLDSLMQFG
Disease Category: Cancer
Disease: Gastric Cancer
Disease Subtype:
Disease Cellline: MGC803
Disease Info:
Drug: HP590
Drug Info: "HP590 is a novel, potent, and orally active STAT3 inhibitor (IC50=27.8 nM for STAT3 luciferase activity; IC50=24.7 nM for ATP inhibition) with anti-proliferative effects against gastric cancer cells and the ability to induce apoptosis. "
Effect: modulate
Effect Info: "The HP590 inhibitor has dual inhibitory activity against p-Tyr705 and p-Ser727. HP590 significantly inhibits the canonical and non-canonical activation of STAT3, resulting in the growth inhibition of gastric cancer cells both in vitro and in vivo."
Note:
Score: 4.0
Pubmed(PMID): 36103247
Sentence Index:
Sentence:

Sequence & Structure:

MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNLLGEIDQQYSRFLQESNVLYQHNLRRIKQFLQSRYLEKPMEIARIVARCLWEESRLLQTAATAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLKSQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEELADWKRRQQIACIGGPPNICLDRLENWITSLAESQLQTRQQIKKLEELQQKVSYKGDPIVQHRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNYQLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGNGGRANCDASLIVTEELHLITFETEVYHQGLKIDLETHSLPVVVISNICQMPNAWASILWYNMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYSGCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILSTKPPGTFLLRFSESSKEGGVTFTWVEKDISGKTQIQSVEPYTKQQLNNMSFAEIIMGYKIMDATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPTTCSNTIDLPMSPRTLDSLMQFGNNGEGAEPSAGGQFESLTFDMELTSECATSPM

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target Drug name MOA Phase Status Disease Source
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 2 Recruiting head and neck squamous cell carcinoma ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 2 Active, not recruiting non-small cell lung carcinoma ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 2 Completed non-small cell lung carcinoma ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 1 Completed hepatocellular carcinoma ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 1 Active, not recruiting head and neck squamous cell carcinoma ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 1 Completed diffuse large B-cell lymphoma ClinicalTrials
ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 1 Active, not recruiting neoplasm ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 1 Active, not recruiting non-small cell lung carcinoma ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 1 Completed non-Hodgkins lymphoma ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 1 Active, not recruiting urinary bladder cancer ClinicalTrials
STAT3 DANVATIRSEN STAT-3 mRNA 3'UTR antisense inhibitor 1 Completed cancer ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets
Small molecule
Antibody
PROTAC
Other modalities
Approved Drug
Advanced Clinical
Phase 1 Clinical
Structure with Ligand
High-Quality Ligand
High-Quality Pocket
Med-Quality Pocket
Druggable Family
Approved Drug
Advanced Clinical
Phase 1 Clinical
UniProt loc high conf
GO CC high conf
UniProt loc med conf
UniProt SigP or TMHMM
GO CC med conf
Human Protein Atlas loc
Approved Drug
Advanced Clinical
Phase 1 Clinical
Literature
UniProt Ubiquitination
Database Ubiquitination
Half-life Data
Small Molecule Binder
Approved Drug
Advanced Clinical
Phase 1 Clinical

PTM Intensity:

source: CPTAC
STAT3-Ser727
Cancer Intensity
BRCA 1.74
COAD
HGSC
ccRCC
GBM -1.099
HNSC
LUAD -0.272
LUSC
non_ccRCC -0.473
PDAC 0.531
UCEC -0.428

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
S 727 D Oral squamous epithelial carcinoma Phosphorylation 23733313
S 727 D Triple-negative breast cancer Phosphorylation 36017196
S 727 D Pancreatic cancer Phosphorylation 37548811
S 727 D Pancreatic cancer/carcinoma/adenocarcinoma Phosphorylation 18519681
S 727 P Prostate cancer/carcinoma/adenocarcinoma Phosphorylation 23941877
S 727 P Breast cancer/tumor/carcinoma Phosphorylation 23329648 ;  23329839
S 727 P Cancer Phosphorylation 23145121
S 727 P Melanoma Phosphorylation 22418867
S 727 U Chronic lymphocytic leukemia Phosphorylation 35595309
S 727 U Clear cell kidney cancer Phosphorylation 24615012 ;  33772065 ;  37945711
S 727 U Head and neck squamous cell carcinoma Phosphorylation 21281788
S 727 U Prostate cancer Phosphorylation 18829527
S 727 U Glioblastoma multiforme Phosphorylation 35670018
S 727 U B-cell acute lymphoblastic leukemia Phosphorylation 33393494
S 727 U Hepatocellular carcinoma Phosphorylation 31498440
S 727 U Thyroid cancer/carcinoma Phosphorylation 17209045

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM
Protein Gene PTM Position Modified sequence Cell Drug pEC50 Regulation Experiment
P40763 STAT3 P Ser727 FICVTPTTCSNTIDLPMS(ph)PR MDA-MB-175 Pertuzumab -4.9774 -
P40763 STAT3 P Ser727 FICVTPTTCSNTIDLPMS(ph)PR MDA-MB-175 Trastuzumab 1.4554 -
P40763 STAT3 P Ser727 TKFICVTPTTCSNTIDLPMS(ph)PR MDA-MB-175 Trastuzumab -0.3231 -
P40763 STAT3 P Ser727 TKFICVTPTTCSNTIDLPMS(ph)PR SK-BR-3 Lapatinib 7.1426 -
P40763 STAT3 P Ser727 FICVTPTTCSNTIDLPMS(ph)PR SK-BR-3 Lapatinib 6.1655 -
P40763 STAT3 P Ser727 FICVTPTTCSNTIDLPMS(ph)PR SK-BR-3 Pertuzumab -1.7721 -
P40763 STAT3 P Ser727 FICVTPTTCSNTIDLPMS(ph)PR SK-BR-3 Trastuzumab 0.8214 -

pEC50 Note: pEC50 is the negative logarithm of EC50 (half-maximal effective concentration, dosage unit Mol), calculated as pEC50 = -log10(EC50), which quantifies the potency of a drug or compound.

Function score:

source: funscoR

No data.

Cross Links: