Proteins > Mitogen-activated protein kinase 12
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Mitogen-activated protein kinase 12
A mitogen-activated protein kinase 12 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P53778]
Synonyms
MAP kinase 12;
MAPK 12;
EC 2.7.11.24;
Extracellular signal-regulated kinase 6;
ERK-6;
Mitogen-activated protein kinase p38 gamma;
MAP kinase p38 gamma;
Stress-activated protein kinase 3
Research
Bioassay Publications (60)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 5 (8.33) | 18.2507 |
| 2000's | 37 (61.67) | 29.6817 |
| 2010's | 17 (28.33) | 24.3611 |
| 2020's | 1 (1.67) | 2.80 |
Compounds (102)
Drugs with Inhibition Measurements
Drugs with Activation Measurements
Design, synthesis and biological evaluation of novel benzimidazole amidines as potent multi-target inhibitors for the treatment of non-small cell lung cancer.European journal of medicinal chemistry, , Jan-01, Volume: 143, 2018
A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.Proceedings of the National Academy of Sciences of the United States of America, , Dec-18, Volume: 104, Issue:51, 2007
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
A small molecule-kinase interaction map for clinical kinase inhibitors.Nature biotechnology, , Volume: 23, Issue:3, 2005
Substituted imidazoles as glucagon receptor antagonists.Bioorganic & medicinal chemistry letters, , Sep-17, Volume: 11, Issue:18, 2001
BREED: Generating novel inhibitors through hybridization of known ligands. Application to CDK2, p38, and HIV protease.Journal of medicinal chemistry, , May-20, Volume: 47, Issue:11, 2004
1-substituted 4-aryl-5-pyridinylimidazoles: a new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency.Journal of medicinal chemistry, , Sep-27, Volume: 39, Issue:20, 1996
From imidazoles to pyrimidines: new inhibitors of cytokine release.Journal of medicinal chemistry, , Jun-20, Volume: 45, Issue:13, 2002
1-substituted 4-aryl-5-pyridinylimidazoles: a new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency.Journal of medicinal chemistry, , Sep-27, Volume: 39, Issue:20, 1996
Design, synthesis and biological evaluation of novel benzimidazole amidines as potent multi-target inhibitors for the treatment of non-small cell lung cancer.European journal of medicinal chemistry, , Jan-01, Volume: 143, 2018
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.European journal of medicinal chemistry, , Jan-01, Volume: 161, 2019
Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors.Bioorganic & medicinal chemistry, , 05-01, Volume: 26, Issue:8, 2018
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
A small molecule-kinase interaction map for clinical kinase inhibitors.Nature biotechnology, , Volume: 23, Issue:3, 2005
Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family.Journal of medicinal chemistry, , Aug-15, Volume: 45, Issue:17, 2002
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A Selective and Brain Penetrant p38αMAPK Inhibitor Candidate for Neurologic and Neuropsychiatric Disorders That Attenuates Neuroinflammation and Cognitive Dysfunction.Journal of medicinal chemistry, , 06-13, Volume: 62, Issue:11, 2019
Discovery of Narrow Spectrum Kinase Inhibitors: New Therapeutic Agents for the Treatment of COPD and Steroid-Resistant Asthma.Journal of medicinal chemistry, , Mar-10, Volume: 59, Issue:5, 2016
KLIFS: a knowledge-based structural database to navigate kinase-ligand interaction space.Journal of medicinal chemistry, , Jan-23, Volume: 57, Issue:2, 2014
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 21, Issue:23, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Trimethylsilylpyrazoles as novel inhibitors of p38 MAP kinase: a new use of silicon bioisosteres in medicinal chemistry.Bioorganic & medicinal chemistry letters, , Jan-15, Volume: 17, Issue:2, 2007
A small molecule-kinase interaction map for clinical kinase inhibitors.Nature biotechnology, , Volume: 23, Issue:3, 2005
Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate.Journal of medicinal chemistry, , Jul-04, Volume: 45, Issue:14, 2002
Recent Developments in the Use of Kinase Inhibitors for Management of Viral Infections.Journal of medicinal chemistry, , 01-27, Volume: 65, Issue:2, 2022
Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer, synthesized from oxygen heterocyclic natural compounds.Bioorganic & medicinal chemistry, , 04-01, Volume: 27, Issue:7, 2019
Synthesis and molecular docking studies of new furochromone derivatives as p38α MAPK inhibitors targeting human breast cancer MCF-7 cells.Bioorganic & medicinal chemistry, , 04-15, Volume: 25, Issue:8, 2017
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Synthesis, biological testing, and binding mode prediction of 6,9-diarylpurin-8-ones as p38 MAP kinase inhibitors.Journal of medicinal chemistry, , May-03, Volume: 50, Issue:9, 2007
The development of novel C-2, C-8, and N-9 trisubstituted purines as inhibitors of TNF-alpha production.Bioorganic & medicinal chemistry letters, , Aug-15, Volume: 16, Issue:16, 2006
A small molecule-kinase interaction map for clinical kinase inhibitors.Nature biotechnology, , Volume: 23, Issue:3, 2005
Development of orally bioavailable bicyclic pyrazolones as inhibitors of tumor necrosis factor-alpha production.Journal of medicinal chemistry, , May-20, Volume: 47, Issue:11, 2004
Kinase inhibitors: not just for kinases anymore.Journal of medicinal chemistry, , Apr-10, Volume: 46, Issue:8, 2003
Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes.Journal of medicinal chemistry, , Jul-17, Volume: 46, Issue:15, 2003
From imidazoles to pyrimidines: new inhibitors of cytokine release.Journal of medicinal chemistry, , Jun-20, Volume: 45, Issue:13, 2002
Identification of novel inhibitors of the transforming growth factor beta1 (TGF-beta1) type 1 receptor (ALK5).Journal of medicinal chemistry, , Feb-28, Volume: 45, Issue:5, 2002
Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate.Journal of medicinal chemistry, , Jul-04, Volume: 45, Issue:14, 2002
Design and synthesis of potent, selective, and orally bioavailable tetrasubstituted imidazole inhibitors of p38 mitogen-activated protein kinase.Journal of medicinal chemistry, , Jun-17, Volume: 42, Issue:12, 1999
Pyrroles and other heterocycles as inhibitors of p38 kinase.Bioorganic & medicinal chemistry letters, , Oct-06, Volume: 8, Issue:19, 1998
Potent inhibitors of the MAP kinase p38.Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 8, Issue:23, 1998
1-substituted 4-aryl-5-pyridinylimidazoles: a new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency.Journal of medicinal chemistry, , Sep-27, Volume: 39, Issue:20, 1996
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
A small molecule-kinase interaction map for clinical kinase inhibitors.Nature biotechnology, , Volume: 23, Issue:3, 2005
General model for estimation of the inhibition of protein kinases using Monte Carlo simulations.Journal of medicinal chemistry, , May-06, Volume: 47, Issue:10, 2004
Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate.Journal of medicinal chemistry, , Jul-04, Volume: 45, Issue:14, 2002
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Why Some Targets Benefit from beyond Rule of Five Drugs.Journal of medicinal chemistry, , 11-27, Volume: 62, Issue:22, 2019
Design, synthesis and biological evaluation of novel benzimidazole amidines as potent multi-target inhibitors for the treatment of non-small cell lung cancer.European journal of medicinal chemistry, , Jan-01, Volume: 143, 2018
A new target for an old drug: identifying mitoxantrone as a nanomolar inhibitor of PIM1 kinase via kinome-wide selectivity modeling.Journal of medicinal chemistry, , Mar-28, Volume: 56, Issue:6, 2013
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
The development of novel C-2, C-8, and N-9 trisubstituted purines as inhibitors of TNF-alpha production.Bioorganic & medicinal chemistry letters, , Aug-15, Volume: 16, Issue:16, 2006
p38 MAP kinase inhibitors. Part 6: 2-arylpyridazin-3-ones as templates for inhibitor design.Bioorganic & medicinal chemistry letters, , Nov-15, Volume: 16, Issue:22, 2006
Hybrid-designed inhibitors of p38 MAP kinase utilizing N-arylpyridazinones.Journal of medicinal chemistry, , Jan-30, Volume: 46, Issue:3, 2003
Design, synthesis and biological evaluation of novel benzimidazole amidines as potent multi-target inhibitors for the treatment of non-small cell lung cancer.European journal of medicinal chemistry, , Jan-01, Volume: 143, 2018
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinJournal of medicinal chemistry, , Nov-16, Volume: 49, Issue:23, 2006
Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays.Journal of medicinal chemistry, , Dec-30, Volume: 47, Issue:27, 2004
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Synthesis, crystal structure, and activity of pyrazole-based inhibitors of p38 kinase.Journal of medicinal chemistry, , Nov-15, Volume: 50, Issue:23, 2007
Synthesis and structure-activity relationship of aminobenzophenones. A novel class of p38 MAP kinase inhibitors with high antiinflammatory activity.Journal of medicinal chemistry, , Dec-18, Volume: 46, Issue:26, 2003
Imidazopyrimidines, potent inhibitors of p38 MAP kinase.Bioorganic & medicinal chemistry letters, , Feb-10, Volume: 13, Issue:3, 2003
Potent inhibitors of the MAP kinase p38.Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 8, Issue:23, 1998
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Pyrimidinylimidazole inhibitors of CSBP/p38 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes.Bioorganic & medicinal chemistry letters, , Nov-17, Volume: 8, Issue:22, 1998
1-substituted 4-aryl-5-pyridinylimidazoles: a new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency.Journal of medicinal chemistry, , Sep-27, Volume: 39, Issue:20, 1996
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor.Science (New York, N.Y.), , Oct-31, Volume: 302, Issue:5646, 2003
Structure-based design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine-based p38 MAP kinase inhibitors.Bioorganic & medicinal chemistry, , 02-01, Volume: 26, Issue:3, 2018
Novel inhibitor of p38 MAP kinase as an anti-TNF-alpha drug: discovery of N-[4-[2-ethyl-4-(3-methylphenyl)-1,3-thiazol-5-yl]-2-pyridyl]benzamide (TAK-715) as a potent and orally active anti-rheumatoid arthritis agent.Journal of medicinal chemistry, , Sep-22, Volume: 48, Issue:19, 2005
Substituted 3-imidazo[1,2-a]pyridin-3-yl- 4-(1,2,3,4-tetrahydro-[1,4]diazepino-[6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3.Journal of medicinal chemistry, , Jul-29, Volume: 47, Issue:16, 2004
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
A quantitative analysis of kinase inhibitor selectivity.Nature biotechnology, , Volume: 26, Issue:1, 2008
Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580.Proceedings of the National Academy of Sciences of the United States of America, , Nov-01, Volume: 102, Issue:44, 2005
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Enables
This protein enables 6 target(s):
| Target | Category | Definition |
|---|
| magnesium ion binding | molecular function | Binding to a magnesium (Mg) ion. [GOC:ai] |
| protein serine/threonine kinase activity | molecular function | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. [GOC:bf, MetaCyc:PROTEIN-KINASE-RXN, PMID:2956925] |
| MAP kinase activity | molecular function | Catalysis of the reaction: protein + ATP = protein phosphate + ADP. This reaction is the phosphorylation of proteins. Mitogen-activated protein kinase; a family of protein kinases that perform a crucial step in relaying signals from the plasma membrane to the nucleus. They are activated by a wide range of proliferation- or differentiation-inducing signals; activation is strong with agonists such as polypeptide growth factors and tumor-promoting phorbol esters, but weak (in most cell backgrounds) by stress stimuli. [GOC:ma, ISBN:0198547684] |
| protein binding | molecular function | Binding to a protein. [GOC:go_curators] |
| ATP binding | molecular function | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. [ISBN:0198506732] |
| protein serine kinase activity | molecular function | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate. [RHEA:17989] |
Located In
This protein is located in 3 target(s):
| Target | Category | Definition |
|---|
| nucleoplasm | cellular component | That part of the nuclear content other than the chromosomes or the nucleolus. [GOC:ma, ISBN:0124325653] |
| mitochondrion | cellular component | A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. [GOC:giardia, ISBN:0198506732] |
| cytosol | cellular component | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. [GOC:hjd, GOC:jl] |
Active In
This protein is active in 2 target(s):
| Target | Category | Definition |
|---|
| nucleus | cellular component | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators] |
| cytoplasm | cellular component | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684] |
Involved In
This protein is involved in 11 target(s):
| Target | Category | Definition |
|---|
| MAPK cascade | biological process | An intracellular protein kinase cascade containing at least a MAP kinase (MAPK). It starts with the activation of a MAP3K, and the consecutive activation of a MPK2K and a MAPK. The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell. [PMID:20811974, PMID:9561267] |
| signal transduction | biological process | The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell. [GOC:go_curators, GOC:mtg_signaling_feb11] |
| muscle organ development | biological process | The process whose specific outcome is the progression of the muscle over time, from its formation to the mature structure. The muscle is an organ consisting of a tissue made up of various elongated cells that are specialized to contract and thus to produce movement and mechanical work. [GOC:jid, ISBN:0198506732] |
| positive regulation of peptidase activity | biological process | Any process that increases the frequency, rate or extent of peptidase activity, the hydrolysis of peptide bonds within proteins. [GOC:dph, GOC:tb] |
| peptidyl-serine phosphorylation | biological process | The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine. [RESID:AA0037] |
| signal transduction in response to DNA damage | biological process | A cascade of processes induced by the detection of DNA damage within a cell. [GOC:go_curators] |
| myoblast differentiation | biological process | The process in which a relatively unspecialized cell acquires specialized features of a myoblast. A myoblast is a mononucleate cell type that, by fusion with other myoblasts, gives rise to the myotubes that eventually develop into striated muscle fibers. [CL:0000056, GOC:go_curators, GOC:mtg_muscle] |
| negative regulation of cell cycle | biological process | Any process that stops, prevents or reduces the rate or extent of progression through the cell cycle. [GOC:dph, GOC:go_curators, GOC:tb] |
| positive regulation of muscle cell differentiation | biological process | Any process that activates or increases the frequency, rate or extent of muscle cell differentiation. [CL:0000187, GOC:ai] |
| regulation of cell cycle | biological process | Any process that modulates the rate or extent of progression through the cell cycle. [GOC:ai, GOC:dph, GOC:tb] |
| intracellular signal transduction | biological process | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. [GOC:bf, GOC:jl, GOC:signaling, ISBN:3527303782] |