Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T65864 | Target Info | |||
| Target 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 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | MAPK14 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | SC-102 | Ligand Info | |||
| Canonical SMILES | C1=CC(=CC=C1C2=C(C=NN2)C3=CC=NC=C3)F | ||||
| InChI | 1S/C14H10FN3/c15-12-3-1-11(2-4-12)14-13(9-17-18-14)10-5-7-16-8-6-10/h1-9H,(H,17,18) | ||||
| InChIKey | BILJSHVAAVZERY-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 12106168 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3HVC Crystal structure of human p38alpha MAP kinase | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [1] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGS37 VCAAFDTKTG47 LRVAVKKLSR57 PFQSIIHAKR 67 TYRELRLLKH77 MKHENVIGLL87 DVFTPARSLE97 EFNDVYLVTH107 LMGADLNNIV 117 LTDDHVQFLI131 YQILRGLKYI141 HSADIIHRDL151 KPSNLAVNED161 CELKILDFGT 185 RWYRAPEIML195 NWMHYNQTVD205 IWSVGCIMAE215 LLTGRTLFPG225 TDHIDQLKLI 235 LRLVGTPGAE245 LLKKISSESA255 RNYIQSLTQM265 PKMNFANVFI275 GANPLAVDLL 285 EKMLVLDSDK295 RITAAQALAH305 AYFAQYHDPD315 DEPVADPYDQ325 SFESRDLLID 335 EWKSLTYDEV345 ISFVPPP
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VAL30
4.889
SER32
4.066
VAL38
3.651
ALA51
3.299
VAL52
4.530
LYS53
3.659
LEU75
4.025
ILE84
4.098
GLY85
4.945
LEU86
3.799
LEU104
3.106
VAL105
3.260
THR106
3.376
HIS107
3.262
LEU108
3.574
MET109
2.675
LEU167
3.726
|
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| PDB ID: 4F9Y Human P38 alpha MAPK In Complex With a Novel and Selective Small Molecule Inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [2] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGA34 YGSVCAAFDT44 KTGLRVAVKK54 LSRPFQSIIH 64 AKRTYRELRL74 LKHMKHENVI84 GLLDVFTPAR94 SLEEFNDVYL104 VTHLMGADLN 114 NIVKCQKLTD124 DHVQFLIYQI134 LRGLKYIHSA144 DIIHRDLKPS154 NLAVNEDCEL 164 KILDFGLAVA184 TRWYRAPEIM194 LNWMHYNQTV204 DIWSVGCIMA214 ELLTGRTLFP 224 GTDHIDQLKL234 ILRLVGTPGA244 ELLKKISSES254 ARNYIQSLTQ264 MPKMNFANVF 274 IGANPLAVDL284 LEKMLVLDSD294 KRITAAQALA304 HAYFAQYHDP314 DDEPVADPYD 324 QSFESRDLLI334 DEWKSLTYDE344 VISFVPPPL
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PRO191
3.808
GLU192
3.670
MET194
3.176
LEU195
3.256
TRP197
3.296
HIS228
3.315
ILE229
3.181
LEU232
3.682
LEU236
3.926
PRO242
3.404
LEU246
3.734
LYS249
3.385
|
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| PDB ID: 4F9W Human P38alpha MAPK in Complex with a Novel and Selective Small Molecule Inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [2] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGA34 YGSVCAAFDT44 KTGLRVAVKK54 LSRPFQSIIH 64 AKRTYRELRL74 LKHMKHENVI84 GLLDVFTPAR94 SLEEFNDVYL104 VTHLMGADLN 114 NIVKCQKLTD124 DHVQFLIYQI134 LRGLKYIHSA144 DIIHRDLKPS154 NLAVNEDCEL 164 KILDFGLATR186 WYRAPEIMLN196 WMHYNQTVDI206 WSVGCIMAEL216 LTGRTLFPGT 226 DHIDQLKLIL236 RLVGTPGAEL246 LKKISSESAR256 NYIQSLTQMP266 KMNFANVFIG 276 ANPLAVDLLE286 KMLVLDSDKR296 ITAAQALAHA306 YFAQYHDPDD316 EPVADPYDQS 326 FESRDLLIDE336 WKSLTYDEVI346 SFVPPP
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PRO191
3.731
GLU192
3.587
MET194
3.170
LEU195
3.334
TRP197
3.256
HIS228
4.239
ILE229
3.761
LEU232
3.913
LEU236
4.007
PRO242
3.529
LEU246
3.605
LYS249
3.192
|
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| PDB ID: 4FA2 Human P38 alpha Mitogen-Activated Kinase In Complex With SB239063 | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [2] |
| PDB Sequence |
ERPTFYRQEL
13 NKTIWEVPER23 YQNLSPVGSG33 AYGSVCAAFD43 TKTGLRVAVK53 KLSRPFQSII 63 HAKRTYRELR73 LLKHMKHENV83 IGLLDVFTPA93 RSLEEFNDVY103 LVTHLMGADL 113 NNIVKCQKLT123 DDHVQFLIYQ133 ILRGLKYIHS143 ADIIHRDLKP153 SNLAVNEDCE 163 LKILDFGLVA184 TRWYRAPEIM194 LNWMHYNQTV204 DIWSVGCIMA214 ELLTGRTLFP 224 GTDHIDQLKL234 ILRLVGTPGA244 ELLKKISSES254 ARNYIQSLTQ264 MPKMNFANVF 274 IGANPLAVDL284 LEKMLVLDSD294 KRITAAQALA304 HAYFAQYHDP314 DDEPVADPYD 324 QSFESRDLLI334 DEWKSLTYDE344 VISFVPPPL
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GG5 or .GG52 or .GG53 or :3GG5;style chemicals stick;color identity;select .A:191 or .A:192 or .A:195 or .A:197 or .A:232 or .A:236 or .A:242 or .A:246 or .A:249 or .A:250 or .A:251 or .A:259 or .A:291 or .A:292 or .A:293 or .A:296; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 4R3C Crystal structure of p38 alpha MAP kinase in complex with a novel isoform selective drug candidate | ||||||
| Method | X-ray diffraction | Resolution | 2.06 Å | Mutation | No | [3] |
| PDB Sequence |
ERPTFYRQEL
13 NKTIWEVPER23 YQNLSPVGSG33 AYGSVCAAFD43 TKTGLRVAVK53 KLSRPFQSII 63 HAKRTYRELR73 LLKHMKHENV83 IGLLDVFTPA93 RSLEEFNDVY103 LVTHLMGADL 113 NNIVKCQKLT123 DDHVQFLIYQ133 ILRGLKYIHS143 ADIIHRDLKP153 SNLAVNEDEL 164 KILDFVATRW187 YRAPEIMLNW197 MHYNQTVDIW207 SVGCIMAELL217 TGRTLFPGTD 227 HIDQLKLILR237 LVGTPGAELL247 KKISSESARN257 YIQSLTQMPK267 MNFANVFIGA 277 NPLAVDLLEK287 MLVLDSDKRI297 TAAQALAHAY307 FAQYHDPDDE317 PVADPYDQSF 327 ESRDLLIDEW337 KSLTYDEVIS347 FVPPP
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GG5 or .GG52 or .GG53 or :3GG5;style chemicals stick;color identity;select .A:191 or .A:192 or .A:195 or .A:197 or .A:232 or .A:236 or .A:242 or .A:246 or .A:249 or .A:250 or .A:251 or .A:259 or .A:291 or .A:292 or .A:293 or .A:296; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4EWQ Human p38 alpha MAPK in complex with a pyridazine based inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [4] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGA34 YGSVCAAFDT44 KTGLRVAVKK54 LSRPFQSIIH 64 AKRTYRELRL74 LKHMKHENVI84 GLLDVFTPAR94 SLEEFNDVYL104 VTHLMGADLN 114 NIVKCQKLTD124 DHVQFLIYQI134 LRGLKYIHSA144 DIIHRDLKPS154 NLAVNEDCEL 164 KILDFARHTD176 DEMGYVATRW187 YRAPEIMLNW197 MHYNQTVDIW207 SVGCIMAELL 217 TGRTLFPGTD227 HIDQLKLILR237 LVGTPGAELL247 KKISSESARN257 YIQSLTQMPK 267 MNFANVFIGA277 NPLAVDLLEK287 MLVLDSDKRI297 TAAQALAHAY307 FAQYHDPDDE 317 PVADPYDQSF327 ESRDLLIDEW337 KSLTYDEVIS347 FVPPPL
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GG5 or .GG52 or .GG53 or :3GG5;style chemicals stick;color identity;select .A:191 or .A:192 or .A:195 or .A:197 or .A:232 or .A:236 or .A:242 or .A:246 or .A:249 or .A:250 or .A:251 or .A:259 or .A:291 or .A:292 or .A:293 or .A:296; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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| PDB ID: 4ZTH Structure of human p38aMAPK-arylpyridazinylpyridine fragment complex used in inhibitor discovery | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [4] |
| PDB Sequence |
ERPTFYRQEL
13 NKTIWEVPER23 YQNLSPVGSG33 AYGSVCAAFD43 TKTGLRVAVK53 KLSRPFQSII 63 HAKRTYRELR73 LLKHMKHENV83 IGLLDVFTPA93 RSLEEFNDVY103 LVTHLMGADL 113 NNIVKCQKLT123 DDHVQFLIYQ133 ILRGLKYIHS143 ADIIHRDLKP153 SNLAVNEDCE 163 LKILDFGLVA184 TRWYRAPEIM194 LNWMHYNQTV204 DIWSVGCIMA214 ELLTGRTLFP 224 GTDHIDQLKL234 ILRLVGTPGA244 ELLKKISSES254 ARNYIQSLTQ264 MPKMNFANVF 274 IGANPLAVDL284 LEKMLVLDSD294 KRITAAQALA304 HAYFAQYHDP314 DDEPVADPYD 324 QSFESRDLLI334 DEWKSLTYDE344 VISFVPPPL
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|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .GG5 or .GG52 or .GG53 or :3GG5;style chemicals stick;color identity;select .A:191 or .A:192 or .A:195 or .A:197 or .A:232 or .A:236 or .A:242 or .A:246 or .A:249 or .A:250 or .A:251 or .A:259 or .A:291 or .A:292 or .A:293 or .A:296; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | p38alpha MAP kinase C-terminal domain binding pocket characterized by crystallographic and computational analyses. J Mol Biol. 2009 Aug 7;391(1):1-11. | ||||
| REF 2 | Development of Novel In Vivo Chemical Probes to Address CNS Protein Kinase Involvement in Synaptic Dysfunction. PLoS One. 2013 Jun 26;8(6):e66226. | ||||
| REF 3 | Targeting human central nervous system protein kinases: An isoform selective p38AlphaMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse models. ACS Chem Neurosci. 2015 Apr 15;6(4):666-80. | ||||
| REF 4 | A Selective and Brain Penetrant p38AlphaMAPK Inhibitor Candidate for Neurologic and Neuropsychiatric Disorders That Attenuates Neuroinflammation and Cognitive Dysfunction. J Med Chem. 2019 Jun 13;62(11):5298-5311. | ||||
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