TTD | Target: T58970

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	P28482
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	[521505], [541019]
	BVD-523	Drug Info	Phase 1/2	Cancer	[524205]
	GDC-0994	Drug Info	Phase 1	Solid tumours	[524324]
	VAN-10-4-eluting stent	Drug Info	Phase 1	Restenosis	[551983]
	SB220025	Drug Info	Terminated	Arthritis	[541295], [546829]
Inhibitor	(4-Fluoro-phenyl)-(9-methyl-9H-purin-6-yl)-amine			Drug Info	[527421]
	4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole			Drug Info	[527308]
	4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol			Drug Info	[528490]
	AEZS-131			Drug Info	[543428]
	BISINDOLYLMALEIMIDE IX			Drug Info	[525872]
	BMS-536924			Drug Info	[527711]
	CHIR-99021			Drug Info	[526553]
	CI-1040			Drug Info	[525872]
	DEBROMOHYMENIALDISINE			Drug Info	[527140]
	ERK inhibitor III			Drug Info	[528449]
	ERK inhibitors			Drug Info	[543428]
	FR-180204			Drug Info	[527815]
	GF-109203			Drug Info	[525872]
	KN-62			Drug Info	[525872]
	KT-5720			Drug Info	[525872]
	Phosphonothreonine			Drug Info	[551393]
	RO-316233			Drug Info	[525872]
	Ro-4396686			Drug Info	[528018]
	SB220025			Drug Info	[551393]
	SCH772984			Drug Info	[532324]
	VAN-10-4-eluting stent			Drug Info	[550172]
Modulator	BVD-523			Drug Info
Modulator	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&#039
	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&amp
	#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 521505	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 524205	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 524324	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 541019	(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).
Ref 541295	(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 546829	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010505)
Ref 551983	Drug-Eluting Stent for High Risk Patients. University of Strathclyde Glasgow. 2015
Ref 525872	Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors.
Ref 526553	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.
Ref 527140	Bioorg Med Chem Lett. 2004 Aug 16;14(16):4319-21.Potent inhibition of checkpoint kinase activity by a hymenialdisine-derived indoloazepine.
Ref 527308	J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole.
Ref 527421	J Med Chem. 2005 Feb 10;48(3):710-22.Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors.
Ref 527711	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.
Ref 527815	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.
Ref 528018	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.
Ref 528449	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.
Ref 528490	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 532324	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.
Ref 543428	(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 550172	WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
Ref 551393	How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

Target Information