General Information of Drug Therapeutic Target (DTT) (ID: TTQBR95)

DTT Name Stress-activated protein kinase 2a (p38 alpha)
Synonyms
SAPK2A; P38 mitogen activatedprotein kinase; P38 Mitogen-activatedprotein kinase alpha; Mitogen-activated protein kinase p38 alpha; Mitogen-activated protein kinase 14; MXI2; MAX-interacting protein 2; MAPK 14; MAP kinase p38alpha; MAP kinase p38 alpha; MAP kinase MXI2; MAP kinase 14; Cytokine suppressive anti-inflammatory drug-binding protein; Cytokine suppressive anti-inflammatory drug binding protein; CSPB1; CSBP2; CSBP1; CSBP; CSAID-binding protein; CSAID binding protein; CRK1
Gene Name MAPK14
DTT Type
Clinical trial target
[1]
BioChemical Class
Kinase
UniProt ID
MK14_HUMAN
TTD ID
T65864
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
EC 2.7.11.24
Sequence
MSQERPTFYRQELNKTIWEVPERYQNLSPVGSGAYGSVCAAFDTKTGLRVAVKKLSRPFQ
SIIHAKRTYRELRLLKHMKHENVIGLLDVFTPARSLEEFNDVYLVTHLMGADLNNIVKCQ
KLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDDEMT
GYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVG
TPGAELLKKISSESARNYIQSLTQMPKMNFANVFIGANPLAVDLLEKMLVLDSDKRITAA
QALAHAYFAQYHDPDDEPVADPYDQSFESRDLLIDEWKSLTYDEVISFVPPPLDQEEMES
Function
MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113'. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway.
KEGG Pathway
MAPK signaling pathway (hsa04010 )
Rap1 signaling pathway (hsa04015 )
FoxO signaling pathway (hsa04068 )
Sphingolipid signaling pathway (hsa04071 )
Adrenergic signaling in cardiomyocytes (hsa04261 )
VEGF signaling pathway (hsa04370 )
Osteoclast differentiation (hsa04380 )
Signaling pathways regulating pluripotency of stem cells (hsa04550 )
Platelet activation (hsa04611 )
Toll-like receptor signaling pathway (hsa04620 )
NOD-like receptor signaling pathway (hsa04621 )
RIG-I-like receptor signaling pathway (hsa04622 )
T cell receptor signaling pathway (hsa04660 )
Fc epsilon RI signaling pathway (hsa04664 )
TNF signaling pathway (hsa04668 )
Leukocyte transendothelial migration (hsa04670 )
Neurotrophin signaling pathway (hsa04722 )
Retrograde endocannabinoid signaling (hsa04723 )
Dopaminergic synapse (hsa04728 )
Inflammatory mediator regulation of TRP channels (hsa04750 )
GnRH signaling pathway (hsa04912 )
Progesterone-mediated oocyte maturation (hsa04914 )
Prolactin signaling pathway (hsa04917 )
Amyotrophic lateral sclerosis (ALS) (hsa05014 )
Epithelial cell signaling in Helicobacter pylori infection (hsa05120 )
Shigellosis (hsa05131 )
Salmonella infection (hsa05132 )
Pertussis (hsa05133 )
Leishmaniasis (hsa05140 )
Chagas disease (American trypanosomiasis) (hsa05142 )
Toxoplasmosis (hsa05145 )
Tuberculosis (hsa05152 )
Hepatitis C (hsa05160 )
Influenza A (hsa05164 )
Epstein-Barr virus infection (hsa05169 )
Proteoglycans in cancer (hsa05205 )
Reactome Pathway
p38MAPK events (R-HSA-171007 )
ERK/MAPK targets (R-HSA-198753 )
Activation of PPARGC1A (PGC-1alpha) by phosphorylation (R-HSA-2151209 )
Oxidative Stress Induced Senescence (R-HSA-2559580 )
CDO in myogenesis (R-HSA-375170 )
DSCAM interactions (R-HSA-376172 )
ADP signalling through P2Y purinoceptor 1 (R-HSA-418592 )
Platelet sensitization by LDL (R-HSA-432142 )
VEGFA-VEGFR2 Pathway (R-HSA-4420097 )
activated TAK1 mediates p38 MAPK activation (R-HSA-450302 )
Activation of the AP-1 family of transcription factors (R-HSA-450341 )
KSRP (KHSRP) binds and destabilizes mRNA (R-HSA-450604 )
NOD1/2 Signaling Pathway (R-HSA-168638 )
BioCyc Pathway
MetaCyc:HS03507-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ozagrel DMIGKA1 Xerophthalmia 5B55.Y Phase 4 [1]
------------------------------------------------------------------------------------
4 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Losmapimod DMIL37Z Acute coronary syndrome BA41 Phase 3 [1]
VX-702 DMKJDR6 Coronary artery disease BA80 Phase 2a [2]
Dilmapimod DMBYJ92 Acute lung injury NB32.3 Phase 2 [1]
VX-745 DMJAEG6 Alzheimer disease 8A20 Phase 2 [3]
------------------------------------------------------------------------------------
6 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PMID25991433-Compound-A1 DM89LF0 N. A. N. A. Patented [4]
PMID25991433-Compound-F2 DM37VIQ N. A. N. A. Patented [4]
PMID25991433-Compound-L1 DM2135Y N. A. N. A. Patented [4]
PMID25991433-Compound-L2 DM58UO9 N. A. N. A. Patented [4]
PMID25991433-Compound-L3 DM3LWUR N. A. N. A. Patented [4]
PMID25991433-Compound-O2 DMTROIQ N. A. N. A. Patented [4]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 Patented Agent(s)
8 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
PAMAPIMOD DM9SYUT Rheumatoid arthritis FA20 Discontinued in Phase 2 [5]
FR167653 DM69OR8 Chronic obstructive pulmonary disease CA22 Discontinued in Phase 1 [6]
R-1487 DM7WPI0 Rheumatoid arthritis FA20 Discontinued in Phase 1 [7]
SB 235699 DMNH8XU Psoriasis vulgaris EA90 Discontinued in Phase 1 [3]
SB-242235 DMKSFL0 Arthritis FA20 Discontinued in Phase 1 [8]
SB 203580 DMAET6F N. A. N. A. Terminated [9]
SB220025 DMSBUET Arthritis FA20 Terminated [10]
SC-102 DM1MQ6Z Solid tumour/cancer 2A00-2F9Z Terminated [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Discontinued Drug(s)
56 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(5-amino-1-phenyl-1H-pyrazol-4-yl)phenylmethanone DMF0YJ3 Discovery agent N.A. Investigative [12]
2-Chlorophenol DM2E3X5 Discovery agent N.A. Investigative [10]
3-(1-NAPHTHYLMETHOXY)PYRIDIN-2-AMINE DMXMBEF Discovery agent N.A. Investigative [11]
3-(Benzyloxy)Pyridin-2-Amine DM35VEI Discovery agent N.A. Investigative [10]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole DMN9YOB Discovery agent N.A. Investigative [13]
4-(2-Ethyl-4-m-tolyl-thiazol-5-yl)-pyridine DMFJW2E Discovery agent N.A. Investigative [14]
4-PHENOXY-N-(PYRIDIN-2-YLMETHYL)BENZAMIDE DMIPQTW Discovery agent N.A. Investigative [11]
4-Phenylsulfanyl-7H-pyrrolo[2,3-d]pyrimidine DMHANXD Discovery agent N.A. Investigative [15]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol DMSKJ1X Discovery agent N.A. Investigative [16]
6-(4-Fluoro-phenylsulfanyl)-9H-purine DM5JWEY Discovery agent N.A. Investigative [15]
6-Benzylsulfanyl-9H-purine DMI7FNZ Discovery agent N.A. Investigative [15]
6-o-tolylquinazolin-2-amine DM4TX9O Discovery agent N.A. Investigative [17]
6-Phenylsulfanyl-9H-purine DMZ76NQ Discovery agent N.A. Investigative [15]
9-(4-Fluoro-benzyl)-6-phenylsulfanyl-9H-purine DMW2NY9 Discovery agent N.A. Investigative [15]
9-Benzyl-6-(4-fluoro-phenylsulfanyl)-9H-purine DM8Q0D9 Discovery agent N.A. Investigative [15]
9-Benzyl-6-phenylsulfanyl-9H-purine DMNCL5G Discovery agent N.A. Investigative [15]
B-Octylglucoside DMMO75G Discovery agent N.A. Investigative [10]
Bisindolylmaleimide-I DMOQJZC Discovery agent N.A. Investigative [18]
CI-1040 DMF3DZX Discovery agent N.A. Investigative [18]
Dihydro-quinolinone DM9UK6D Discovery agent N.A. Investigative [19]
DP-802 DMARTC2 Inflammation 1A00-CA43.1 Investigative [20]
GSK-280 DM325YR Inflammation 1A00-CA43.1 Investigative [20]
GW-788388 DMIBUW5 Solid tumour/cancer 2A00-2F9Z Investigative [21]
IN-1130 DM3YJXF Discovery agent N.A. Investigative [22]
IN-1166 DMMS6D3 Discovery agent N.A. Investigative [22]
KN-62 DMLZ89P Discovery agent N.A. Investigative [18]
KT-5720 DM9J50F Discovery agent N.A. Investigative [18]
L-779450 DM51B74 Discovery agent N.A. Investigative [23]
ML-3163 DM3S5UC Discovery agent N.A. Investigative [24]
ML-3375 DMXJY6W Discovery agent N.A. Investigative [25]
ML-3403 DMTQWI8 Discovery agent N.A. Investigative [25]
N-(3-(trifluoromethoxy)benzyl)-4-phenoxybenzamide DM6UC8Y Discovery agent N.A. Investigative [26]
N-(3-(trifluoromethyl)benzyl)-4-phenoxybenzamide DMSMRF9 Discovery agent N.A. Investigative [26]
N-(4-(trifluoromethyl)benzyl)-4-phenoxybenzamide DMZ0V8O Discovery agent N.A. Investigative [26]
N-(4-fluorobenzyl)-N-(pyridin-4-yl)-2-naphthamide DMP1ICB Discovery agent N.A. Investigative [27]
N-(4-methyl-benzyl)-4-phenoxy-benzamide DMZX2BH Discovery agent N.A. Investigative [26]
Oxindole 94 DMPFD6Y Pain MG30-MG3Z Investigative [28]
PD-0166326 DMD2CG9 Discovery agent N.A. Investigative [29]
PD-0173956 DM8RW92 Discovery agent N.A. Investigative [29]
PHA-666859 DMHQ6KT Diabetic retinopathy 9B71.0 Investigative [20]
Phenyl-(3-phenyl-1H-indazol-6-yl)-amine DMDCTNU Discovery agent N.A. Investigative [30]
PMID22521646C12 DMYQDXO Discovery agent N.A. Investigative [31]
RO-316233 DMAGLPW Discovery agent N.A. Investigative [18]
Ro-3201195 DM9GXYV Discovery agent N.A. Investigative [32]
Ro31-8220 DMDJLF0 Discovery agent N.A. Investigative [18]
RWJ-68354 DMNLVRS Discovery agent N.A. Investigative [33]
SB-216995 DMOH9TA Discovery agent N.A. Investigative [19]
SB-218655 DMJKE4M Discovery agent N.A. Investigative [19]
SB-227931 DMO1WI8 Discovery agent N.A. Investigative [34]
Small molecule 34 DMWJ70Q Discovery agent N.A. Investigative [10]
STAUROSPORINONE DMU2H4K Discovery agent N.A. Investigative [18]
Talmapimod DMMTSL2 Discovery agent N.A. Investigative [35]
Triazolopyridine DM1F2K0 Discovery agent N.A. Investigative [11]
Tyrphostin ag-1478 DM87ZIH Discovery agent N.A. Investigative [36]
UCB-1277763 DMFUE43 Inflammation 1A00-CA43.1 Investigative [20]
ZM-336372 DMD5JYQ Discovery agent N.A. Investigative [37]
------------------------------------------------------------------------------------
⏷ Show the Full List of 56 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Coronary artery disease BA80-BA8Z Peripheral blood 4.57E-01 -0.55 -0.55
Psoriasis EA90 Skin 4.95E-14 0.48 1.09
Rheumatoid arthritis FA20 Synovial tissue 7.98E-04 1.33 2.48
Chronic obstructive pulmonary disease CA23 Lung tissue 7.60E-01 -0.01 -0.02
Chronic obstructive pulmonary disease CA23 Small airway epithelium 6.17E-03 -0.26 -0.49
------------------------------------------------------------------------------------

References

1 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
2 Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
3 Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
4 c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
5 Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. J Med Chem. 2010 Mar 25;53(6):2345-53.
6 Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum. 2003 Sep;48(9):2670-81.
7 Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38alpha mitogen-activated protein kinase. J Med Chem. 2011 Apr 14;54(7):2255-65.
8 Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4433-7.
9 The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment. Blood. 2001 Aug 1;98(3):667-73.
10 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
11 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
12 Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxypropoxy)phenyl]methanone (RO3201195), an orally bioavailable and highl... J Med Chem. 2006 Mar 9;49(5):1562-75.
13 Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
14 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 (T... J Med Chem. 2005 Sep 22;48(19):5966-79.
15 Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. J Med Chem. 2005 Feb 10;48(3):710-22.
16 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
17 Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity. J Med Chem. 2006 Sep 21;49(19):5671-86.
18 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
19 In silico search for multi-target anti-inflammatories in Chinese herbs and formulas. Bioorg Med Chem. 2010 Mar 15;18(6):2204-2218.
20 URL: 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: 1499).
21 Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orall... J Med Chem. 2006 Apr 6;49(7):2210-21.
22 Synthesis and biological evaluation of trisubstituted imidazole derivatives as inhibitors of p38alpha mitogen-activated protein kinase. Bioorg Med Chem Lett. 2008 Jul 15;18(14):4006-10.
23 The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
24 From imidazoles to pyrimidines: new inhibitors of cytokine release. J Med Chem. 2002 Jun 20;45(13):2733-40.
25 Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J Med Chem. 2003 Jul 17;46(15):3230-44.
26 Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5274-9.
27 Amide-based inhibitors of p38alpha MAP kinase. Part 2: design, synthesis and SAR of potent N-pyrimidyl amides. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2560-3.
28 Inhibition of p38 MAPK decreases myocardial TNF-alpha expression and improves myocardial function and survival in endotoxemia. Cardiovasc Res. 2003 Oct 1;59(4):893-900.
29 Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6.
30 Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3. Bioorg Med Chem Lett. 2005 Nov 15;15(22):5095-9.
31 Novel triazolopyridylbenzamides as potent and selective p38alpha inhibitors. Bioorg Med Chem Lett. 2012 May 15;22(10):3431-6.
32 Microwave-assisted synthesis of 5-aminopyrazol-4-yl ketones and the p38(MAPK) inhibitor RO3201195 for study in Werner syndrome cells. Bioorg Med Chem Lett. 2008 Jul 1;18(13):3745-8.
33 Imidazopyrimidines, potent inhibitors of p38 MAP kinase. Bioorg Med Chem Lett. 2003 Feb 10;13(3):347-50.
34 The neuroprotective action of JNK3 inhibitors based on the 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole scaffold. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4666-70.
35 Mitogen-activated protein kinases in innate immunity.Nat Rev Immunol.2013 Sep;13(9):679-92.
36 Novel, potent and selective anilinoquinazoline and anilinopyrimidine inhibitors of p38 MAP kinase. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5389-94.
37 A novel series of p38 MAP kinase inhibitors for the potential treatment of rheumatoid arthritis. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5383-7.