| Id: | acc1946 |
| Group: | 2sens |
| Protein: | STAT3 |
| Gene Symbol: | STAT3 |
| Protein Id: | P40763 |
| Protein Name: | STAT3_HUMAN |
| PTM: | phosphorylation |
| Site: | Tyr705 |
| Site Sequence: | EADPGSAAPYLKTKFICVTPT |
| Disease Category: | Cancer |
| Disease: | Colorectal Cancer |
| Disease Subtype: | |
| Disease Cellline: | HCT116 |
| Disease Info: | |
| Drug: | B12 |
| Drug Info: | "Cyanocobalamin is a synthetic form of vitamin B12 used to treat and prevent vitamin B12 deficiency, including pernicious anemia, dietary deficiency, and malabsorption syndromes." |
| Effect: | modulate |
| Effect Info: | B12 induces apoptosis and inhibits the migration of cancer cells by suppressing the phosphorylation at the Tyr705 site and the expression of STAT3 downstream genes. |
| Note: | |
| Score: | 4.0 |
| Pubmed(PMID): | 33774344 |
| Sentence Index: | 33774344_4-5 |
| Sentence: | "Compound B12, the best active compound of this series, was identified as an inhibitor of IL-6/STAT3 signaling with an IC50 of 0.61-1.11 muM in MDA-MB-231, HCT-116 and SW480 tumor cell lines with STAT3 overexpression, by inhibiting the phosphorylation of STAT3 of Tyr705 residue and the expression of STAT3 downstream genes, inducing apoptosis and inhibiting the migration of cancer cells. Furthermore, in vivo study revealed that compound B12 suppressed the MDA-MB-231 xenograft tumor growth in nude mice at the dose of 30 mg/kg (i.g.), which has better antitumor activity than the positive control Niclosamide." |
Sequence & Structure:
MAQWNQLQQLDTRYLEQLHQLYSDSFPMELRQFLAPWIESQDWAYAASKESHATLVFHNLLGEIDQQYSRFLQESNVLYQHNLRRIKQFLQSRYLEKPMEIARIVARCLWEESRLLQTAATAAQQGGQANHPTAAVVTEKQQMLEQHLQDVRKRVQDLEQKMKVVENLQDDFDFNYKTLKSQGDMQDLNGNNQSVTRQKMQQLEQMLTALDQMRRSIVSELAGLLSAMEYVQKTLTDEELADWKRRQQIACIGGPPNICLDRLENWITSLAESQLQTRQQIKKLEELQQKVSYKGDPIVQHRPMLEERIVELFRNLMKSAFVVERQPCMPMHPDRPLVIKTGVQFTTKVRLLVKFPELNYQLKIKVCIDKDSGDVAALRGSRKFNILGTNTKVMNMEESNNGSLSAEFKHLTLREQRCGNGGRANCDASLIVTEELHLITFETEVYHQGLKIDLETHSLPVVVISNICQMPNAWASILWYNMLTNNPKNVNFFTKPPIGTWDQVAEVLSWQFSSTTKRGLSIEQLTTLAEKLLGPGVNYSGCQITWAKFCKENMAGKGFSFWVWLDNIIDLVKKYILALWNEGYIMGFISKERERAILSTKPPGTFLLRFSESSKEGGVTFTWVEKDISGKTQIQSVEPYTKQQLNNMSFAEIIMGYKIMDATNILVSPLVYLYPDIPKEEAFGKYCRPESQEHPEADPGSAAPYLKTKFICVTPTTCSNTIDLPMSPRTLDSLMQFGNNGEGAEPSAGGQFESLTFDMELTSECATSPM
Select PDB:
| 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 TargetsPTM Intensity:
source: CPTAC| STAT3-Tyr705 | |
|---|---|
| Cancer | Intensity |
| BRCA | 0.868 |
| COAD | |
| HGSC | |
| ccRCC | |
| GBM | 0.383 |
| HNSC | |
| LUAD | -0.032 |
| LUSC | |
| non_ccRCC | -1.398 |
| PDAC | 1.121 |
| UCEC | -0.942 |
PTM-Disease Association:
source: PTMD| Residue | Position | State | Disease | Class | PMID |
|---|---|---|---|---|---|
| Y | 705 | D | Triple-negative breast cancer | Phosphorylation | 36017196 |
| Y | 705 | D | Inflammatory disease | Phosphorylation | 24063605 |
| Y | 705 | N | Bladder cancer | Phosphorylation | 18939995 |
| Y | 705 | P | Breast cancer/tumor/carcinoma | Phosphorylation | 23350355 ; 22374428 ; 23446809 |
| Y | 705 | P | Colon cancer/carcinoma | Phosphorylation | 22754353 ; 21840932 |
| Y | 705 | U | Experimental autoimmune encephalomyelitis | Phosphorylation | 32094172 |
| Y | 705 | U | Laryngeal cancer | Phosphorylation | 27181202 |
| Y | 705 | U | Lung cancer | Phosphorylation | 34543857 |
| Y | 705 | U | Malignant gliomas | Phosphorylation | 23740516 |
| Y | 705 | U | Multiple sclerosis | Phosphorylation | 32094172 |
| Y | 705 | U | Myeloma | Phosphorylation | 22210382 |
| Y | 705 | U | Neurofibromatosis | Phosphorylation | 23318430 |
| Y | 705 | U | Non-Hodgkin's lymphoma | Phosphorylation | 30054295 |
| Y | 705 | U | Prostate cancer | Phosphorylation | 19147545 ; 19147545 |
| Y | 705 | U | T-cell lymphoma | Phosphorylation | 35882439 |
| Y | 705 | U | Fibrosarcoma | Phosphorylation | 21575192 |
| Y | 705 | U | Head and neck squamous cell carcinoma | Phosphorylation | 21281788 |
| Y | 705 | U | Esophageal carcinoma | Phosphorylation | 33986510 |
| Y | 705 | U | Clear cell kidney cancer | Phosphorylation | 24615012 |
| Y | 705 | U | Acute myelogenous leukemia | Phosphorylation | 34525179 |
| Y | 705 | U | B-cell lymphoma | Phosphorylation | 22116549 |
| Y | 705 | U | Breast cancer | Phosphorylation | 17967179 ; 17967179 ; 18353781 ; 35927628 |
| Y | 705 | U | Esophageal squamous cell carcinoma | Phosphorylation | 23676499 |
| Y | 705 | U | Triple-negative breast cancer | Phosphorylation | 34066153 ; 35091679 |
| Y | 705 | U | Pancreatic cancer | Phosphorylation | 37548811 ; 36374556 |
| Y | 705 | U | Colorectal cancer | Phosphorylation | 36266267 |
| Y | 705 | U | Glioblastoma | Phosphorylation | 34411567 ; 20455003 |
| Y | 705 | U | Melanoma | Phosphorylation | 35184394 ; 22899991 |
| Y | 705 | U | Multiple myeloma | Phosphorylation | 34782371 |
| Y | 705 | U | Breast cancer/tumor/carcinoma | Phosphorylation | 24707243 |
| Y | 705 | U | Cancer | Phosphorylation | 23145121 |
| Y | 705 | U | Colon adenocarcinoma | Phosphorylation | 34270850 |
| Y | 705 | U | Hepatocellular carcinoma/hepatocarcinoma/hepatoma | Phosphorylation | 21311975 |
| Y | 705 | U | Pancreatic cancer/carcinoma/adenocarcinoma | Phosphorylation | 18519681 |
| Y | 705 | U | Prostate cancer/carcinoma/adenocarcinoma | Phosphorylation | 22307624 ; 19147545 |
| Y | 705 | U | Renal cancer/carcinoma | Phosphorylation | 22982675 |
| Y | 705 | U | Renal cell carcinoma | Phosphorylation | 22899991 |
| Y | 705 | U | Bladder cancer | Phosphorylation | 34326684 |
| Y | 705 | U | Glioblastoma multiforme | Phosphorylation | 35670018 |
| Y | 705 | U | Nasopharyngeal carcinoma | Phosphorylation | 33824475 |
| Y | 705 | U | Hepatocellular carcinoma | Phosphorylation | 22153071 |
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: DecryptMNo data.
Function score:
source: funscoRNo data.
