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mitogen-activated protein kinase 14

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1499

Nomenclature: mitogen-activated protein kinase 14

Abbreviated Name: p38α

Family: p38 subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 360 6p21.31 MAPK14 mitogen-activated protein kinase 14
Mouse - 360 17 14.85 cM Mapk14 mitogen-activated protein kinase 14
Rat - 360 20p12 Mapk14 mitogen activated protein kinase 14
Previous and Unofficial Names Click here for help
CRK1 | Csaids binding protein | CSBP | CSBP1 | CSBP2 | CSPB1 | Cytokine suppressive anti-inflammatory drug binding protein | Exip | Hog | MAPK 14 | MAP kinase 14 | MAP kinase 2 | MAP kinase Mxi2 | MAP kinase p38 alpha | MAX-interacting protein 2 | mitogen-activated protein kinase 14A | mitogen-activated protein kinase p38 alpha | Mxi2 | p38αMAPK | p38 MAPK | p38 MAP kinase alpha | p38 mitogen activated protein kinase | PRKM14 | PRKM15 | Sapk2A | stress-activated protein kinase 2A
Database Links Click here for help
Alphafold Q16539 (Hs), P47811 (Mm), P70618 (Rn)
BRENDA 2.7.11.24
ChEMBL Target CHEMBL260 (Hs), CHEMBL2336 (Mm), CHEMBL4825 (Rn)
Ensembl Gene ENSG00000112062 (Hs), ENSMUSG00000053436 (Mm), ENSRNOG00000000513 (Rn)
Entrez Gene 1432 (Hs), 26416 (Mm), 81649 (Rn)
Human Protein Atlas ENSG00000112062 (Hs)
KEGG Enzyme 2.7.11.24
KEGG Gene hsa:1432 (Hs), mmu:26416 (Mm), rno:81649 (Rn)
OMIM 600289 (Hs)
Pharos Q16539 (Hs)
RefSeq Nucleotide NM_001315 (Hs), NM_001168508 (Mm), NM_031020 (Rn)
RefSeq Protein NP_001306 (Hs), NP_001161985 (Mm), NP_001161980 (Mm), NP_001161986 (Mm), NP_036081 (Mm), NP_112282 (Rn)
SynPHARM 80146 (in complex with AZD6703)
80672 (in complex with BMS-582949)
85089 (in complex with pamapimod)
80641 (in complex with PH-797804)
78583 (in complex with SB203580)
80561 (in complex with SB220025)
83879 (in complex with TAK-715)
80639 (in complex with talmapimod)
81051 (in complex with VX-745)
UniProtKB Q16539 (Hs), P47811 (Mm), P70618 (Rn)
Wikipedia MAPK14 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human p38alpha complexed with PH-797804
PDB Id:  3HLL
Ligand:  PH-797804
Resolution:  1.95Å
Species:  Human
References:  40
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of p38 MAPKα in complex with BMS-582949
PDB Id:  3MVL
Ligand:  BMS-582949
Resolution:  2.8Å
Species:  Human
References:  28
Image of receptor 3D structure from RCSB PDB
Description:  P38 kinase crystal structure in complex with pamapimod.
PDB Id:  3FLW
Ligand:  pamapimod
Resolution:  2.1Å
Species:  Human
References:  22
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of p38 alpha MAP kinase in complex with a novel isoform selective drug candidate
PDB Id:  4R3C
Ligand:  MW150
Resolution:  2.06Å
Species:  Human
References:  36
Enzyme Reaction Click here for help
EC Number: 2.7.11.24

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PF-03715455 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Binding 12.0 pKd 30
⤷ pKd 12.0 (Kd 1x10-12 M) [30]
doramapimod Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.4 pKd 16
⤷ pKd 9.4 (Kd 4.5x10-10 M) [16]
pamapimod Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.9 pKd 22
⤷ pKd 8.9 (Kd 1.3x10-9 M) [22]
Description: In a biochemical assay.
VX-702 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.4 pKd 21
⤷ pKd 8.4 (Kd 3.7x10-9 M) [21]
PH-797804 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.5 pKi
⤷ pKi 8.5 (Ki 2.9x10-9 M)
losmapimod Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 8.1 pKi 9
⤷ pKi 8.1 (Ki 7.94x10-9 M) [9]
SB203580 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.0 pKi 17
⤷ pKi 8.0 (Ki 1x10-8 M) [17]
MW150 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.0 pKi 7,36
⤷ pKi 7.0 (Ki 1.01x10-7 M) [7,36]
Description: Ki determined from a TR-FRET based (LanthaScreen®) kinase binding assay, which analysed competitive binding to the non-activated form of p38α MAPK.
AZD7624 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 10.0 pIC50 14
⤷ pIC50 10.0 (IC50 1x10-10 M) [14]
compound 4e [PMID: 35546685] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 10.0 pIC50 8
⤷ pIC50 10.0 (IC50 1x10-10 M) [8]
compound 12 [PMID: 22521646] Small molecule or natural product Primary target of this compound Hs Inhibition 9.2 pIC50 3
⤷ pIC50 9.2 (IC50 6.4x10-10 M) [3]
PF-03715455 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 30
⤷ pIC50 9.1 (IC50 8.8x10-10 M) [30]
ARRY-371797 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 21
⤷ pIC50 8.4 (IC50 4.5x10-9 M) [21]
Description: In vitro enzyme inhibition assay.
ralimetinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 – 8.4 pIC50 13,29
⤷ pIC50 8.4 (IC50 4x10-9 M) [13]
pIC50 8.1 (IC50 7x10-9 M) [29]
TAK-715 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 31
⤷ pIC50 8.1 (IC50 7.1x10-9 M) [31]
talmapimod Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 pIC50 37
⤷ pIC50 8.1 (IC50 9x10-9 M) [37]
neflamapimod Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.0 pIC50 25
⤷ pIC50 8.0 (IC50 1x10-8 M) [25]
BMS-582949 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 28
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [28]
AZD6703 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.8 pIC50 15
⤷ pIC50 7.8 (IC50 1.558x10-8 M) [15]
SB220025 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.7 pIC50 1
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [1]
doramapimod Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.7 pIC50 32
⤷ pIC50 7.7 (IC50 2x10-8 M) [32]
SB202190 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.5 pIC50 20
⤷ pIC50 7.5 (IC50 3x10-8 M) [20]
pexmetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pIC50 10
⤷ pIC50 7.5 (IC50 3.5x10-8 M) [10]
7-hydroxystaurosporine Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 35
⤷ pIC50 7.0 (IC50 9.5x10-8 M) [35]
NDPPC Small molecule or natural product Hs Inhibition 7.0 pIC50
⤷ pIC50 7.0 (IC50 1x10-7 M)
SKF-86002 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.0 pIC50 26
⤷ pIC50 7.0 (IC50 1.1x10-7 M) [26]
Description: Measured using a classic homogeneous time-resolved fluorescence (HTRF) kinase assay
PF-670462 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.7 pIC50 11
⤷ pIC50 6.7 (IC50 1.9x10-7 M) [11]
Description: In a biochemical kinase assay.
CBS-3595 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.3 pIC50 4
⤷ pIC50 6.3 (IC50 5x10-7 M) [4]
Description: In vitro determination.
PP1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pIC50 12
⤷ pIC50 6.2 (IC50 6.4x10-7 M) [12]
acumapimod Small molecule or natural product Immunopharmacology Ligand Hs Inhibition >6.0 pIC50 18
⤷ pIC50 >6.0 (IC50 <1x10-6 M) [18]
MAPK13-IN-1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.4 pIC50 5
⤷ pIC50 5.4 (IC50 3.6x10-6 M) [5]
dilmapimod Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition >5.0 pIC50 2
⤷ pIC50 >5.0 (IC50 <1x10-5 M) [2]
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 16,39
Key to terms and symbols Click column headers to sort
Target used in screen: p38-alpha
Ligand Sp. Type Action Value Parameter
doramapimod Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.4 pKd
neflamapimod Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.6 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 7.9 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.6 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 6,19
Key to terms and symbols Click column headers to sort
Target used in screen: SAPK2a/P38a(MAPK14)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
VX-702 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 5.2
SB202190 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.4 1.0 1.0
p38 MAP kinase inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 7.6 -1.0 0.0
PD 169316 Small molecule or natural product Hs Inhibitor Inhibition 7.8 1.0 2.0
p38 MAP kinase inhibitor Small molecule or natural product Hs Inhibitor Inhibition 11.2 3.0 0.0
SB220025 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 13.1 2.0 1.0
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 22.8 5.0 2.0
nilotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 23.3
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 36.5
sorafenib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 40.2
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
p38 MAP kinases are ubiquitous, highly conserved enzymes which regulate the production of proinflammatory mediators (such as TNFα and IL-1) in response to inflammatory cytokines or environmental stress [23-24,27,33-34,38]. They are essential for normal immune and inflammatory responses, but are also involved in many other cellular processes such as regulating the cell cycle and cytoskeletal remodelling.

Pharmacological inhibition of p38 MAP kinases reduces inflammatory cytokine synthesis, making these enzymes validated and extensively pursued drug targets for autoimmune and inflammatory diseases, including arthritis and other joint diseases, septic shock, myocardial injury and neuroinflammation. A number of pan-p38 MAP kinase inhibitors and isoform selective inhibitors have been evaluated in clinical trials.

MAPK14 is ubiquitously expressed and its central role in pro-inflammatory signalling made it a popular drug target for chronic inflammatory diseases. However, MAPK14 inhibitors have failed to show clinical efficacy, most likely due to MAPK14's wide-spread tissue distrubution and/or off-target effects on other kinases. It is worth noting that knockout of Mapk14 in mice is embryonic lethal.
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Tissue repair

References

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1. Adams JL, Boehm JC, Gallagher TF, Kassis S, Webb EF, Hall R, Sorenson M, Garigipati R, Griswold DE, Lee JC. (2001) Pyrimidinylimidazole inhibitors of p38: cyclic N-1 imidazole substituents enhance p38 kinase inhibition and oral activity. Bioorg Med Chem Lett, 11 (21): 2867-70. [PMID:11597418]

2. Adams JL, Boehm JC, Hall R, Jin Q, Kasparec J, Silva DJ, Taggart JJ. Novel trisubstituted-8H-pyrido[2,3-d]pyrimidin-7-one compound for the treatment of CSBP/p38 kinase mediated diseases. Patent number: EP1333833. Assignee: GlaxoSmithKline LLC. Priority date: 23/10/2000. Publication date: 23/10/2001.

3. Aiguadé J, Balagué C, Carranco I, Caturla F, Domínguez M, Eastwood P, Esteve C, González J, Lumeras W, Orellana A et al.. (2012) Novel triazolopyridylbenzamides as potent and selective p38α inhibitors. Bioorg Med Chem Lett, 22 (10): 3431-6. [PMID:22521646]

4. Albrecht W, Unger A, Bauer SM, Laufer SA. (2017) Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases. J Med Chem, 60 (13): 5290-5305. [PMID:28613871]

5. Alevy YG, Patel AC, Romero AG, Patel DA, Tucker J, Roswit WT, Miller CA, Heier RF, Byers DE, Brett TJ et al.. (2012) IL-13-induced airway mucus production is attenuated by MAPK13 inhibition. J Clin Invest, 122 (12): 4555-68. [PMID:23187130]

6. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

7. Arancio O, Watterson DM, Pelletier JC, Roy SM. (2014) Map kinase modulators and uses thereof. Patent number: WO2014145485A2. Assignee: The Trustees Of Columbia University In The City Of New York. Priority date: 15/03/2013. Publication date: 18/09/2014.

8. Armani E, Capaldi C, Bagnacani V, Saccani F, Aquino G, Puccini P, Facchinetti F, Martucci C, Moretto N, Villetti G et al.. (2022) Design, Synthesis, and Biological Characterization of Inhaled p38α/β MAPK Inhibitors for the Treatment of Lung Inflammatory Diseases. J Med Chem, 65 (10): 7170-7192. [PMID:35546685]

9. Aston NM, Bamborough P, Buckton JB, Edwards CD, Holmes DS, Jones KL, Patel VK, Smee PA, Somers DO, Vitulli G et al.. (2009) p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression. J Med Chem, 52 (20): 6257-69. [PMID:19772287]

10. Bachegowda L, Morrone K, Winski SL, Mantzaris I, Bartenstein M, Ramachandra N, Giricz O, Sukrithan V, Nwankwo G, Shahnaz S et al.. (2016) Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Cancer Res, 76 (16): 4841-4849. [PMID:27287719]

11. Badura L, Swanson T, Adamowicz W, Adams J, Cianfrogna J, Fisher K, Holland J, Kleiman R, Nelson F, Reynolds L et al.. (2007) An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions. J Pharmacol Exp Ther, 322 (2): 730-8. [PMID:17502429]

12. Bain J, McLauchlan H, Elliott M, Cohen P. (2003) The specificities of protein kinase inhibitors: an update. Biochem J, 371 (Pt 1): 199-204. [PMID:12534346]

13. Bhattacharjee D, Bakar J, Chitnis SP, Sausville EL, Ashtekar KD, Mendelson BE, Long K, Smith JC, Heppner DE, Sheltzer JM. (2023) Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor. Cell Chem Biol, 30 (10): 1211-1222.e5. [PMID:37827156]

14. Brough S, Evans R, Luker TJ, Raubo P. (2008) Pyrazinone derivatives and their use in the treatment of lung diseases. Patent number: WO2009001132A1. Assignee: Astrazeneca. Priority date: 27/06/2007. Publication date: 31/12/2008.

15. Brown DS, Cumming JG, Bethel P, Finlayson J, Gerhardt S, Nash I, Pauptit RA, Pike KG, Reid A, Snelson W et al.. (2012) The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide (AZD6703), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases. Bioorg Med Chem Lett, 22 (12): 3879-83. [PMID:22608965]

16. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

17. Eyers PA, Craxton M, Morrice N, Cohen P, Goedert M. (1998) Conversion of SB 203580-insensitive MAP kinase family members to drug-sensitive forms by a single amino-acid substitution. Chem Biol, 5 (6): 321-8. [PMID:9653550]

18. Fryszman OM, Lang H, Lan J, Chang E, Fang Y. (2005) 5-membered heterocycle-based p38 kinase inhibitors. Patent number: WO2005009973. Assignee: Novartis Ag. Priority date: 26/06/2003. Publication date: 03/02/2005.

19. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

20. Goldstein DM, Alfredson T, Bertrand J, Browner MF, Clifford K, Dalrymple SA, Dunn J, Freire-Moar J, Harris S, Labadie SS et al.. (2006) Discovery of S-[5-amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]-[3-(2,3-dihydroxypropoxy)phenyl]methanone (RO3201195), an orally bioavailable and highly selective inhibitor of p38 MAP kinase. J Med Chem, 49 (5): 1562-75. [PMID:16509574]

21. Goldstein DM, Kuglstatter A, Lou Y, Soth MJ. (2010) Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. J Med Chem, 53 (6): 2345-53. [PMID:19950901]

22. Goldstein DM, Soth M, Gabriel T, Dewdney N, Kuglstatter A, Arzeno H, Chen J, Bingenheimer W, Dalrymple SA, Dunn J et al.. (2011) 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 p38α mitogen-activated protein kinase. J Med Chem, 54 (7): 2255-65. [PMID:21375264]

23. Han J, Jiang Y, Li Z, Kravchenko VV, Ulevitch RJ. (1997) Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation. Nature, 386 (6622): 296-9. [PMID:9069290]

24. Han J, Lee JD, Bibbs L, Ulevitch RJ. (1994) A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science, 265 (5173): 808-11. [PMID:7914033]

25. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT et al.. (2008) A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol, 26 (1): 127-32. [PMID:18183025]

26. Klüter S, Grütter C, Naqvi T, Rabiller M, Simard JR, Pawar V, Getlik M, Rauh D. (2010) Displacement assay for the detection of stabilizers of inactive kinase conformations. J Med Chem, 53 (1): 357-67. [PMID:19928858]

27. Lee JC, Kumar S, Griswold DE, Underwood DC, Votta BJ, Adams JL. (2000) Inhibition of p38 MAP kinase as a therapeutic strategy. Immunopharmacology, 47 (2-3): 185-201. [PMID:10878289]

28. Liu C, Lin J, Wrobleski ST, Lin S, Hynes J, Wu H, Dyckman AJ, Li T, Wityak J, Gillooly KM et al.. (2010) Discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a clinical p38α MAP kinase inhibitor for the treatment of inflammatory diseases. J Med Chem, 53 (18): 6629-39. [PMID:20804198]

29. Mader M, de Dios A, Shih C, Bonjouklian R, Li T, White W, López de Uralde B, Sánchez-Martinez C, del Prado M, Jaramillo C et al.. (2008) Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38alpha MAP kinase inhibitors with excellent in vivo antiinflammatory properties. Bioorg Med Chem Lett, 18 (1): 179-83. [PMID:18039577]

30. Millan DS, Bunnage ME, Burrows JL, Butcher KJ, Dodd PG, Evans TJ, Fairman DA, Hughes SJ, Kilty IC, Lemaitre A et al.. (2011) Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease. J Med Chem, 54 (22): 7797-814. [PMID:21888439]

31. Miwatashi S, Arikawa Y, Kotani E, Miyamoto M, Naruo K, Kimura H, Tanaka T, Asahi S, Ohkawa S. (2005) 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. J Med Chem, 48 (19): 5966-79. [PMID:16162000]

32. Moffett K, Konteatis Z, Nguyen D, Shetty R, Ludington J, Fujimoto T, Lee KJ, Chai X, Namboodiri H, Karpusas M et al.. (2011) Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD). Bioorg Med Chem Lett, 21 (23): 7155-65. [PMID:22014550]

33. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH. (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev, 22 (2): 153-83. [PMID:11294822]

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p38 subfamily: mitogen-activated protein kinase 14. Last modified on 13/10/2023. Accessed on 23/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1499.