Id: acc2057
Group: 2sens
Protein: ERK1
Gene Symbol: MAPK3
Protein Id: P27361
Protein Name: MK03_HUMAN
PTM: phosphorylation
Site: Tyr204
Site Sequence: HDHTGFLTEYVATRWYRAPEI
Disease Category: Cancer
Disease: Lung Cancer
Disease Subtype:
Disease Cellline: HCC2450
Disease Info:
Drug: AZD6244
Drug Info: AZD6244 (Selumetinib) is a selective MEK1/MEK2 inhibitor developed by AstraZeneca for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas and certain advanced cancers such as non-small cell lung cancer.
Effect: modulate
Effect Info: Treatment with AZD6244 inhibited ERK phosphorylation in both sensitive and drug-resistant cells.
Note:
Score: 4.0
Pubmed(PMID): 19783898
Sentence Index:
Sentence:

Sequence & Structure:

MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDLKICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSDSKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target Drug name MOA Phase Status Disease Source
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 2 Terminated neoplasm ClinicalTrials
MAPK3 TEMUTERKIB Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 2 Completed pancreatic carcinoma ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 2 Recruiting histiocytic neoplasm ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 2 Active, not recruiting Uveal Melanoma ClinicalTrials
MAPK3 TEMUTERKIB Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 2 Terminated cancer ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Completed acute myeloid leukemia ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Completed myelodysplastic syndrome ClinicalTrials
MAPK3 TEMUTERKIB Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 1 Recruiting acute myeloid leukemia ClinicalTrials
MAPK3 RAVOXERTINIB MAP kinase ERK1 inhibitor 1 Completed neoplasm ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Completed neoplasm ClinicalTrials
ClinicalTrials
MAPK3 MK-8353 MAP kinase ERK1 inhibitor 1 Completed neoplasm ClinicalTrials
MAPK3 MK-8353 MAP kinase ERK1 inhibitor 1 Terminated neoplasm ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Recruiting pancreatic carcinoma ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Terminated pancreatic carcinoma ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Recruiting metastatic colorectal cancer ClinicalTrials
MAPK3 KO-947 Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 1 Terminated cancer ClinicalTrials
MAPK3 MK-8353 MAP kinase ERK1 inhibitor 1 Completed colorectal cancer ClinicalTrials
MAPK3 TEMUTERKIB Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 0.5 Recruiting glioblastoma multiforme ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 0.5 Recruiting Paraganglioma 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
MAPK3-Tyr204
Cancer Intensity
BRCA 1.299
COAD 0.294
HGSC 1.686
ccRCC -0.456
GBM 0.155
HNSC 0.082
LUAD -0.027
LUSC 0.328
non_ccRCC -0.355
PDAC -1.055
UCEC -1.949

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
Y 204 D Acute lymphocytic leukemia Phosphorylation 26073130
Y 204 D Head and neck squamous cell carcinoma Phosphorylation 21281788
Y 204 U Breast cancer Phosphorylation 31944568
Y 204 U Acute myelogenous leukemia Phosphorylation 26073130
Y 204 U Alzheimer's disease Phosphorylation 35847683
Y 204 U Glioma Phosphorylation 33820494
Y 204 U Pulmonary emphysema Phosphorylation 14764579
Y 204 U Triple-negative breast cancer Phosphorylation 28415597
Y 204 U Tuberous sclerosis complex Phosphorylation 17671177

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
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR BT-474 Lapatinib 6.5402 down
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR MDA-MB-175 Lapatinib 7.4061 down
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR MDA-MB-175 Pertuzumab -4.6099 down
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR BT-474 Pertuzumab -1.9536 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR BT-474 Trastuzumab -1.9524 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR MDA-MB-175 Trastuzumab 5 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR SK-BR-3 Lapatinib 6.25 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR SK-BR-3 Pertuzumab -1.7417 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR SK-BR-3 Trastuzumab -0.8941 -

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: