Target General Infomation |
Target ID |
T58970
|
Former ID |
TTDR00372
|
Target Name |
Mitogen-activated protein kinase 1
|
Gene Name |
MAPK1
|
Synonyms |
ERK-2; ERT1; Extracellular signal-regulated kinase 2; MAP kinase 2; MAPK 2; Mitogen-activated protein kinase 2; P42 Mitogen-activated protein kinase; P42-MAPK; MAPK1
|
Target Type |
Clinical Trial
|
Disease |
Arthritis [ICD9: 710-719; ICD10: M00-M25] |
Cancer [ICD9: 140-229; ICD10: C00-C96] |
Restenosis [ICD10: I51.89] |
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] |
Function |
Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.
|
BioChemical Class |
Kinase
|
Target Validation |
T58970
|
UniProt ID |
|
EC Number |
EC 2.7.11.24
|
Sequence |
MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFE HQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQH LSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDH TGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHI LGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHK RIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS
|
Drugs and Mode of Action |
Drug(s) |
CI-1040 |
Drug Info |
Phase 2 |
Discovery agent |
[1],
[2] |
BVD-523 |
Drug Info |
Phase 1/2 |
Cancer |
[3] |
GDC-0994 |
Drug Info |
Phase 1 |
Solid tumours |
[4] |
VAN-10-4-eluting stent |
Drug Info |
Phase 1 |
Restenosis |
[5] |
SB220025 |
Drug Info |
Terminated |
Arthritis |
[6],
[7] |
Inhibitor |
(4-Fluoro-phenyl)-(9-methyl-9H-purin-6-yl)-amine |
Drug Info |
[8] |
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole |
Drug Info |
[9] |
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol |
Drug Info |
[10] |
AEZS-131 |
Drug Info |
[11] |
BISINDOLYLMALEIMIDE IX |
Drug Info |
[12] |
BMS-536924 |
Drug Info |
[13] |
CHIR-99021 |
Drug Info |
[14] |
CI-1040 |
Drug Info |
[12] |
DEBROMOHYMENIALDISINE |
Drug Info |
[15] |
ERK inhibitor III |
Drug Info |
[16] |
ERK inhibitors |
Drug Info |
[11] |
FR-180204 |
Drug Info |
[17] |
GF-109203 |
Drug Info |
[12] |
KN-62 |
Drug Info |
[12] |
KT-5720 |
Drug Info |
[12] |
Phosphonothreonine |
Drug Info |
[18] |
RO-316233 |
Drug Info |
[12] |
Ro-4396686 |
Drug Info |
[19] |
SB220025 |
Drug Info |
[18] |
SCH772984 |
Drug Info |
[20] |
VAN-10-4-eluting stent |
Drug Info |
[21] |
Modulator |
BVD-523 |
Drug Info |
|
GDC-0994 |
Drug Info |
|
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) |
TEP |
EXP Info
|
Pathways |
KEGG Pathway
|
MAPK signaling pathway
|
ErbB signaling pathway
|
Ras signaling pathway
|
Rap1 signaling pathway
|
cGMP-PKG signaling pathway
|
cAMP signaling pathway
|
Chemokine signaling pathway
|
HIF-1 signaling pathway
|
FoxO signaling pathway
|
Sphingolipid signaling pathway
|
Oocyte meiosis
|
mTOR signaling pathway
|
PI3K-Akt signaling pathway
|
Adrenergic signaling in cardiomyocytes
|
Vascular smooth muscle contraction
|
Dorso-ventral axis formation
|
TGF-beta signaling pathway
|
Axon guidance
|
VEGF signaling pathway
|
Osteoclast differentiation
|
Focal adhesion
|
Adherens junction
|
Gap junction
|
Signaling pathways regulating pluripotency of stem cells
|
Platelet activation
|
Toll-like receptor signaling pathway
|
NOD-like receptor signaling pathway
|
Natural killer cell mediated cytotoxicity
|
T cell receptor signaling pathway
|
B cell receptor signaling pathway
|
Fc epsilon RI signaling pathway
|
Fc gamma R-mediated phagocytosis
|
TNF signaling pathway
|
Circadian entrainment
|
Long-term potentiation
|
Neurotrophin signaling pathway
|
Retrograde endocannabinoid signaling
|
Glutamatergic synapse
|
Cholinergic synapse
|
Serotonergic synapse
|
Long-term depression
|
Regulation of actin cytoskeleton
|
Insulin signaling pathway
|
GnRH signaling pathway
|
Progesterone-mediated oocyte maturation
|
Estrogen signaling pathway
|
Melanogenesis
|
Prolactin signaling pathway
|
Thyroid hormone signaling pathway
|
Oxytocin signaling pathway
|
Type II diabetes mellitus
|
Aldosterone-regulated sodium reabsorption
|
Alzheimer'
|
s disease
|
Prion diseases
|
Alcoholism
|
Shigellosis
|
Salmonella infection
|
Pertussis
|
Leishmaniasis
|
Chagas disease (American trypanosomiasis)
|
Toxoplasmosis
|
Tuberculosis
|
Hepatitis C
|
Hepatitis B
|
Influenza A
|
Pathways in cancer
|
Viral carcinogenesis
|
Proteoglycans in cancer
|
MicroRNAs in cancer
|
Colorectal cancer
|
Renal cell carcinoma
|
Pancreatic cancer
|
Endometrial cancer
|
Glioma
|
Prostate cancer
|
Thyroid cancer
|
Melanoma
|
Bladder cancer
|
Chronic myeloid leukemia
|
Acute myeloid leukemia
|
Non-small cell lung cancer
|
Central carbon metabolism in cancer
|
Choline metabolism in cancer
|
NetPath Pathway
|
IL2 Signaling Pathway
|
PANTHER Pathway
|
Alzheimer disease-amyloid secretase pathway
|
Angiogenesis
|
Apoptosis signaling pathway
|
B cell activation
|
EGF receptor signaling pathway
|
Endothelin signaling pathway
|
FGF signaling pathway
|
Inflammation mediated by chemokine and cytokine signaling pathway
|
Insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade
|
Interferon-gamma signaling pathway
|
Interleukin signaling pathway
|
PDGF signaling pathway
|
Parkinson disease
|
TGF-beta signaling pathway
|
T cell activation
|
VEGF signaling pathway
|
Ras Pathway
|
Angiotensin II-stimulated signaling through G proteins and beta-arrestin
|
CCKR signaling map ST
|
Pathway Interaction Database
|
Fc-epsilon receptor I signaling in mast cells
|
Endothelins
|
BCR signaling pathway
|
Signaling events mediated by PRL
|
ErbB4 signaling events
|
GMCSF-mediated signaling events
|
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
|
S1P3 pathway
|
EPHB forward signaling
|
Osteopontin-mediated events
|
S1P4 pathway
|
Presenilin action in Notch and Wnt signaling
|
TRAIL signaling pathway
|
CDC42 signaling events
|
Signaling events regulated by Ret tyrosine kinase
|
Angiopoietin receptor Tie2-mediated signaling
|
S1P1 pathway
|
Regulation of Telomerase
|
Netrin-mediated signaling events
|
Glucocorticoid receptor regulatory network
|
Arf6 downstream pathway
|
mTOR signaling pathway
|
Class IB PI3K non-lipid kinase events
|
IL2-mediated signaling events
|
EGF receptor (ErbB1) signaling pathway
|
Ras signaling in the CD4+ TCR pathway
|
Ceramide signaling pathway
|
Integrins in angiogenesis
|
IFN-gamma pathway
|
ErbB1 downstream signaling
|
ATF-2 transcription factor network
|
ErbB2/ErbB3 signaling events
|
BMP receptor signaling
|
ALK1 signaling events
|
PDGFR-beta signaling pathway
|
Neurotrophic factor-mediated Trk receptor signaling
|
Syndecan-1-mediated signaling events
|
Retinoic acid receptors-mediated signaling
|
Nongenotropic Androgen signaling
|
CXCR3-mediated signaling events
|
VEGFR1 specific signals
|
Regulation of cytoplasmic and nuclear SMAD2/3 signaling
|
Signaling events mediated by VEGFR1 and VEGFR2
|
Syndecan-2-mediated signaling events
|
Cellular roles of Anthrax toxin
|
S1P2 pathway
|
Trk receptor signaling mediated by the MAPK pathway
|
Downstream signaling in na&
|
#xef
|
ve CD8+ T cells
|
VEGFR3 signaling in lymphatic endothelium
|
Alpha-synuclein signaling
|
FGF signaling pathway
|
Signaling events mediated by focal adhesion kinase
|
PathWhiz Pathway
|
Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
|
Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
|
Fc Epsilon Receptor I Signaling in Mast Cells
|
Insulin Signalling
|
Reactome
|
RAF-independent MAPK1/3 activation
|
MAPK1 (ERK2) activation
|
Golgi Cisternae Pericentriolar Stack Reorganization
|
ERK/MAPK targets
|
Regulation of actin dynamics for phagocytic cup formation
|
Oxidative Stress Induced Senescence
|
Senescence-Associated Secretory Phenotype (SASP)
|
Oncogene Induced Senescence
|
FCERI mediated MAPK activation
|
Regulation of HSF1-mediated heat shock response
|
NCAM signaling for neurite out-growth
|
Recycling pathway of L1
|
CREB phosphorylation through the activation of Ras
|
Activation of the AP-1 family of transcription factors
|
Thrombin signalling through proteinase activated receptors (PARs)
|
Negative regulation of FGFR1 signaling
|
Negative regulation of FGFR2 signaling
|
Negative regulation of FGFR3 signaling
|
Negative regulation of FGFR4 signaling
|
RHO GTPases Activate WASPs and WAVEs
|
RAF/MAP kinase cascade
|
MAP2K and MAPK activation
|
Negative feedback regulation of MAPK pathway
|
Negative regulation of MAPK pathway
|
Signal attenuation
|
Advanced glycosylation endproduct receptor signaling
|
Gastrin-CREB signalling pathway via PKC and MAPK
|
Growth hormone receptor signaling
|
WikiPathways
|
Toll-like receptor signaling pathway
|
Serotonin Receptor 4/6/7 and NR3C Signaling
|
Serotonin Receptor 2 and ELK-SRF/GATA4 signaling
|
Serotonin HTR1 Group and FOS Pathway
|
Vitamin A and Carotenoid Metabolism
|
DNA Damage Response (only ATM dependent)
|
TCR Signaling Pathway
|
ErbB Signaling Pathway
|
Hypothetical Network for Drug Addiction
|
Senescence and Autophagy in Cancer
|
EPO Receptor Signaling
|
Regulation of Actin Cytoskeleton
|
IL-2 Signaling Pathway
|
Insulin Signaling
|
EGF/EGFR Signaling Pathway
|
MAPK Cascade
|
IL-4 Signaling Pathway
|
MAPK Signaling Pathway
|
TGF beta Signaling Pathway
|
IL-6 signaling pathway
|
Signaling of Hepatocyte Growth Factor Receptor
|
Kit receptor signaling pathway
|
TCA Cycle Nutrient Utilization and Invasiveness of Ovarian Cancer
|
Apoptosis-related network due to altered Notch3 in ovarian cancer
|
IL-3 Signaling Pathway
|
Bladder Cancer
|
Cardiac Hypertrophic Response
|
MAP kinase activation in TLR cascade
|
Fc epsilon receptor (FCERI) signaling
|
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
|
RAF/MAP kinase cascade
|
Nanoparticle-mediated activation of receptor signaling
|
Structural Pathway of Interleukin 1 (IL-1)
|
Genes and (Common) Pathways Underlying Drug Addiction
|
EBV LMP1 signaling
|
Signal Transduction of S1P Receptor
|
Nifedipine Activity
|
Aryl Hydrocarbon Receptor
|
PDGF Pathway
|
Alpha 6 Beta 4 signaling pathway
|
Spinal Cord Injury
|
BDNF signaling pathway
|
Integrated Pancreatic Cancer Pathway
|
Oncostatin M Signaling Pathway
|
Corticotropin-releasing hormone
|
Interleukin-11 Signaling Pathway
|
AGE/RAGE pathway
|
TNF alpha Signaling Pathway
|
B Cell Receptor Signaling Pathway
|
Prostate Cancer
|
Signaling Pathways in Glioblastoma
|
TSLP Signaling Pathway
|
IL-9 Signaling Pathway
|
Endothelin Pathways
|
IL17 signaling pathway
|
Alzheimers Disease
|
IL-7 Signaling Pathway
|
TWEAK Signaling Pathway
|
FSH signaling pathway
|
Leptin signaling pathway
|
RANKL/RANK Signaling Pathway
|
Integrated Breast Cancer Pathway
|
Opioid Signalling
|
IL-1 signaling pathway
|
Thrombin signalling through proteinase activated receptors (PARs)
|
Signaling by FGFR
|
Integrin-mediated Cell Adhesion
|
L1CAM interactions
|
Advanced glycosylation endproduct receptor signaling
|
Heart Development
|
Type II diabetes mellitus
|
MicroRNAs in cardiomyocyte hypertrophy
|
Angiogenesis
|
Physiological and Pathological Hypertrophy of the Heart
|
Regulation of toll-like receptor signaling pathway
|
Osteopontin Signaling
|
IL-5 Signaling Pathway
|
References |
REF 1 | ClinicalTrials.gov (NCT00033384) CI-1040 in Treating Patients With Advanced Breast, Colon, Pancreatic, or Non-Small Cell Lung Cancer. U.S. National Institutes of Health. |
---|
REF 2 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5676). |
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REF 3 | ClinicalTrials.gov (NCT01781429) Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies. U.S. National Institutes of Health. |
---|
REF 4 | ClinicalTrials.gov (NCT01875705) A Dose-Escalation Study of GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health. |
---|
REF 5 | Drug-Eluting Stent for High Risk Patients. University of Strathclyde Glasgow. 2015 |
---|
REF 6 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6038). |
---|
REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010505) |
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REF 8 | J Med Chem. 2005 Feb 10;48(3):710-22.Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. |
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REF 9 | J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. |
---|
REF 10 | J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. |
---|
REF 11 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1495). |
---|
REF 12 | Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors. |
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REF 13 | J Med Chem. 2005 Sep 8;48(18):5639-43.Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. |
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REF 14 | Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95. |
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REF 15 | Bioorg Med Chem Lett. 2004 Aug 16;14(16):4319-21.Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine. |
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REF 16 | Characterization of ATP-independent ERK inhibitors identified through in silico analysis of the active ERK2 structure. Bioorg Med Chem Lett. 2006 Dec 15;16(24):6281-7. Epub 2006 Sep 26. |
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REF 17 | Bioorg Med Chem Lett. 2006 Jan 1;16(1):55-8. Epub 2005 Oct 18.Crystal structure of human ERK2 complexed with a pyrazolo[3,4-c]pyridazine derivative. |
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REF 18 | How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. |
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REF 19 | Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3. Epub 2006 Feb 3.Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. |
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REF 20 | Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-50. |
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REF 21 | WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting. |