| Id: | acc1871 |
| Group: | 2sens |
| Protein: | ERK1 |
| Gene Symbol: | MAPK3 |
| Protein Id: | P27361 |
| Protein Name: | MK03_HUMAN |
| PTM: | phosphorylation |
| Site: | Thr202 |
| Site Sequence: | PEHDHTGFLTEYVATRWYRAP |
| Disease Category: | Cancer |
| Disease: | Colorectal Cancer |
| Disease Subtype: | |
| Disease Cellline: | SW480 |
| Disease Info: | |
| Drug: | PD98059 + rapamycin |
| Drug Info: | "PD98059 is a non-ATP competitive MEK inhibitor with an IC50 of 2 μM, specifically inhibiting MEK-1-mediated MAPK activation without directly suppressing ERK1 and ERK2. rapamycin: -" |
| Effect: | modulate |
| Effect Info: | Drug treatment reduces the phosphorylation level and inhibits tumors. |
| Note: | drug comb |
| Score: | 4.0 |
| Pubmed(PMID): | 19194827 |
| Sentence Index: | 19194827_2-3 |
| Sentence: | "Here, we found that combination treatment with PD98059 and rapamycin suppressed the proliferation of CRC cells, induced apoptosis, arrested cell cycle, and reduced the incidence and volume of CRC in mice, as well as inhibited phosphorylation of mTOR and the MEK signal pathway components, of which the effects were more significant than single-drug treatments. These findings indicate that PD98059 combined with rapamycin appears to be a promising strategy for inhibiting the initiation, and progression of CRC, which may provide a novel strategy for CRC prevention." |
Sequence & Structure:
MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDLKICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSDSKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP
Select PDB:
| 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 TargetsPTM Intensity:
source: CPTAC| MAPK3-Thr202 | |
|---|---|
| Cancer | Intensity |
| BRCA | 2.637 |
| COAD | -0.058 |
| HGSC | 0.315 |
| ccRCC | -0.838 |
| GBM | -0.198 |
| HNSC | -0.165 |
| LUAD | 0 |
| LUSC | 0.376 |
| non_ccRCC | -1.222 |
| PDAC | -0.124 |
| UCEC | -0.724 |
PTM-Disease Association:
source: PTMD| Residue | Position | State | Disease | Class | PMID |
|---|---|---|---|---|---|
| T | 202 | D | Acute lymphocytic leukemia | Phosphorylation | 26073130 |
| T | 202 | D | Head and neck squamous cell carcinoma | Phosphorylation | 21281788 |
| T | 202 | U | Pulmonary emphysema | Phosphorylation | 14764579 |
| T | 202 | U | Acute myelogenous leukemia | Phosphorylation | 26073130 |
| T | 202 | U | Alzheimer's disease | Phosphorylation | 35847683 |
| T | 202 | U | Glioma | Phosphorylation | 33820494 |
| T | 202 | U | Breast cancer | Phosphorylation | 31944568 |
| T | 202 | U | Hepatocellular carcinoma | Phosphorylation | 36230524 |
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 | Thr202 | IADPEHDHTGFLT(ph)EYVATR | BT-474 | Pertuzumab | -1.9738 | - | |
| P27361 | MAPK3 | P | Thr202 | IADPEHDHTGFLT(ph)EYVATR | MDA-MB-175 | Trastuzumab | -5.405 | - |
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: funscoRNo data.
