Target General Infomation
Target ID
T55729
Former ID
TTDR00352
Target Name
Mitogen-activated protein kinase 11
Gene Name
MAPK11
Synonyms
MAP kinase p38 beta; Mitogen-activated protein kinase p38 beta; P38 Mitogen-activated protein kinase beta; P38-2; P38b; Stress-activated protein kinase-2; MAPK11
Target Type
Clinical Trial
Disease Psoriasis [ICD9: 696; ICD10: L40]
Function
Kinase involved in a signal transduction pathway that is activated by changes in the osmolarity of the extracellular environment, by cytokines, or by environmental stress. Phosphorylates preferentially transcription factor atf2.
BioChemical Class
Kinase
Target Validation
T55729
UniProt ID
EC Number
EC 2.7.11.24
Sequence
MSGPRAGFYRQELNKTVWEVPQRLQGLRPVGSGAYGSVCSAYDARLRQKVAVKKLSRPFQ
SLIHARRTYRELRLLKHLKHENVIGLLDVFTPATSIEDFSEVYLVTTLMGADLNNIVKCQ
ALSDEHVQFLVYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQADEEMT
GYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLQGKALFPGSDYIDQLKRIMEVVG
TPSPEVLAKISSEHARTYIQSLPPMPQKDLSSIFRGANPLAIDLLGRMLVLDSDQRVSAA
EALAHAYFSQYHDPEDEPEAEPYDESVEAKERTLEEWKELTYQEVLSFKPPEPPKPPGSL
EIEQ
Drugs and Mode of Action
Drug(s) CI-1040 Drug Info Phase 2 Discovery agent [521505], [541019]
SB 235699 Drug Info Discontinued in Phase 1 Psoriasis [547031]
Inhibitor 4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole Drug Info [527308]
BISINDOLYLMALEIMIDE IX Drug Info [525872]
CI-1040 Drug Info [525872]
GF-109203 Drug Info [525872]
KN-62 Drug Info [525872]
KT-5720 Drug Info [525872]
L-779450 Drug Info [527836]
ML-3163 Drug Info [526355]
ML-3375 Drug Info [526668]
ML-3403 Drug Info [526668]
RO-316233 Drug Info [525872]
RWJ-68354 Drug Info [526530]
SB 235699 Drug Info [535353]
STAUROSPORINONE Drug Info [525872]
Vertex 745 (VX745) Drug Info [535353]
VK-19911 Drug Info [526904]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway MAPK signaling pathway
Rap1 signaling pathway
FoxO signaling pathway
Sphingolipid signaling pathway
Adrenergic signaling in cardiomyocytes
VEGF signaling pathway
Osteoclast differentiation
Signaling pathways regulating pluripotency of stem cells
Platelet activation
Toll-like receptor signaling pathway
NOD-like receptor signaling pathway
RIG-I-like receptor signaling pathway
T cell receptor signaling pathway
Fc epsilon RI signaling pathway
TNF signaling pathway
Leukocyte transendothelial migration
Neurotrophin signaling pathway
Retrograde endocannabinoid signaling
Dopaminergic synapse
Inflammatory mediator regulation of TRP channels
GnRH signaling pathway
Progesterone-mediated oocyte maturation
Prolactin signaling pathway
Amyotrophic lateral sclerosis (ALS)
Epithelial cell signaling in Helicobacter pylori infection
Shigellosis
Salmonella infection
Pertussis
Leishmaniasis
Chagas disease (American trypanosomiasis)
Toxoplasmosis
Tuberculosis
Hepatitis C
Influenza A
Epstein-Barr virus infection
Proteoglycans in cancer
PANTHER Pathway Alzheimer disease-amyloid secretase pathway
B cell activation
EGF receptor signaling pathway
FGF signaling pathway
Interferon-gamma signaling pathway
Oxidative stress response
TGF-beta signaling pathway
Ras Pathway
p53 pathway feedback loops 2
p38 MAPK pathway
Pathway Interaction Database p73 transcription factor network
p38 MAPK signaling pathway
Plasma membrane estrogen receptor signaling
CD40/CD40L signaling
Regulation of p38-alpha and p38-beta
FAS (CD95) signaling pathway
Thromboxane A2 receptor signaling
Glucocorticoid receptor regulatory network
IL2-mediated signaling events
Rapid glucocorticoid signaling
ATF-2 transcription factor network
IL6-mediated signaling events
p38 signaling mediated by MAPKAP kinases
CXCR3-mediated signaling events
Signaling mediated by p38-alpha and p38-beta
Signaling events mediated by VEGFR1 and VEGFR2
VEGFR3 signaling in lymphatic endothelium
Regulation of retinoblastoma protein
PathWhiz Pathway Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Reactome NOD1/2 Signaling Pathway
p38MAPK events
ERK/MAPK targets
Activation of PPARGC1A (PGC-1alpha) by phosphorylation
Oxidative Stress Induced Senescence
CDO in myogenesis
DSCAM interactions
VEGFA-VEGFR2 Pathway
activated TAK1 mediates p38 MAPK activation
Activation of the AP-1 family of transcription factors
KSRP (KHSRP) binds and destabilizes mRNA
WikiPathways Toll-like receptor signaling pathway
Insulin Signaling
IL-4 Signaling Pathway
MAP kinase activation in TLR cascade
Regulation of mRNA Stability by Proteins that Bind AU-rich Elements
Nanoparticle-mediated activation of receptor signaling
Structural Pathway of Interleukin 1 (IL-1)
Parkinsons Disease Pathway
NGF signalling via TRKA from the plasma membrane
Myogenesis
DSCAM interactions
Physiological and Pathological Hypertrophy of the Heart
Regulation of toll-like receptor signaling pathway
References
Ref 521505ClinicalTrials.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 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 547031Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012315)
Ref 525872Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors.
Ref 526355J Med Chem. 2002 Jun 20;45(13):2733-40.From imidazoles to pyrimidines: new inhibitors of cytokine release.
Ref 526530Bioorg Med Chem Lett. 2003 Feb 10;13(3):347-50.Imidazopyrimidines, potent inhibitors of p38 MAP kinase.
Ref 526668J Med Chem. 2003 Jul 17;46(15):3230-44.Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes.
Ref 526904J Med Chem. 2003 Dec 18;46(26):5651-62.Synthesis and structure-activity relationship of aminobenzophenones. A novel class of p38 MAP kinase inhibitors with high antiinflammatory activity.
Ref 527308J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole.
Ref 527836Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81. Epub 2005 Nov 2.The identification of potent and selective imidazole-based inhibitors of B-Raf kinase.
Ref 535353Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.

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