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 | 2-Fluoro-4-[4-(4-Fluorophenyl)-1h-Pyrazol-3-Yl]pyridine | Ligand Info | |||
| Canonical SMILES | C1=CC(=CC=C1C2=C(NN=C2)C3=CC(=NC=C3)F)F | ||||
| InChI | 1S/C14H9F2N3/c15-11-3-1-9(2-4-11)12-8-18-19-14(12)10-5-6-17-13(16)7-10/h1-8H,(H,18,19) | ||||
| InChIKey | YJCHZVXSPFPKMX-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 42647299 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3HL7 Crystal Structure of Human p38alpha complexed with SD-0006 | ||||||
| Method | X-ray diffraction | Resolution | 1.88 Å | Mutation | No | [1] |
| PDB Sequence |
PTFYRQELNK
14 TIWEVPERYQ24 NLSPVGSGAY34 GSVCAAFDTK44 TGLRVAVKKL54 SRPFQSIIHA 64 KRTYRELRLL74 KHMKHENVIG84 LLDVFTPARS94 LEEFNDVYLV104 THLMGADLNN 114 IVKCQKLTDD124 HVQFLIYQIL134 RGLKYIHSAD144 IIHRDLKPSN154 LAVNEDCELK 164 ILDFGLAATR185 WYRAPEIMLN195 WMHYNQTVDI205 WSVGCIMAEL215 LTGRTLFPGT 225 DHIDQLKLIL235 RLVGTPGAEL245 LKKISSESAR255 NYIQSLTQMP265 KMNFANVFIG 275 ANPLAVDLLE285 KMLVLDSDKR295 ITAAQALAHA305 YFAQYHDPDD315 EPVADPYDQS 325 FESRDLLIDE335 WKSLTYDEVI345 SFVPPP
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| PDB ID: 3HLL Crystal Structure of Human p38alpha complexed with PH-797804 | ||||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [1] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGA34 YGSVCAAFDT44 KTGLRVAVKK54 LSRPFQSIIH 64 AKRTYRELRL74 LKHMKHENVI84 GLLDVFTPAR94 SLEEFNDVYL104 VTHLMGADLN 114 NIVKCQKLTD124 DHVQFLIYQI134 LRGLKYIHSA144 DIIHRDLKPS154 NLAVNEDCEL 164 KILDFGLVAT185 RWYRAPEIML195 NWMHYNQTVD205 IWSVGCIMAE215 LLTGRTLFPG 225 TDHIDQLKLI235 LRLVGTPGAE245 LLKKISSESA255 RNYIQSLTQM265 PKMNFANVFI 275 GANPLAVDLL285 EKMLVLDSDK295 RITAAQALAH305 AYFAQYHDPD315 DEPVADPYDQ 325 SFESRDLLID335 EWKSLTYDEV345 ISFVPPP
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| PDB ID: 3HP2 Crystal Structure of Human p38alpha complexed with a pyridinone compound | ||||||
| Method | X-ray diffraction | Resolution | 2.15 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 VISFVPPPLD354 Q
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| PDB ID: 3HP5 Crystal Structure of Human p38alpha complexed with a pyrimidopyridazinone compound | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [2] |
| PDB Sequence |
PTFYRQELNK
15 TIWEVPERYQ25 NLSPVGSVCA40 AFDTKTGLRV50 AVKKLSRPFQ60 SIIHAKRTYR 70 ELRLLKHMKH80 ENVIGLLDVF90 TPARSLEEFN100 DVYLVTHLMG110 ADLNNIVKCQ 120 KLTDDHVQFL130 IYQILRGLKY140 IHSADIIHRD150 LKPSNLAVNE160 DCELKILDFG 170 VATRWYRAPE192 IMLNWMHYNQ202 TVDIWSVGCI212 MAELLTGRTL222 FPGTDHIDQL 232 KLILRLVGTP242 GAELLKKISS252 ESARNYIQSL262 TQMPKMNFAN272 VFIGANPLAV 282 DLLEKMLVLD292 SDKRITAAQA302 LAHAYFAQYH312 DPDDEPVADP322 YDQSFESRDL 332 LIDEWKSLTY342 DEVISFVPPP352
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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 .I46 or .I462 or .I463 or :3I46;style chemicals stick;color identity;select .A:22 or .A:23 or .A:25 or .A:42 or .A:44 or .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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GLU22
2.958
ARG23
4.234
GLN25
3.631
PHE42
4.868
THR44
3.428
PRO191
3.891
GLU192
3.718
LEU195
3.578
TRP197
3.307
LEU232
4.085
LEU236
4.403
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| PDB ID: 2YIS triazolopyridine inhibitors of p38 kinase. | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGS37 VCAAFDTKTG47 LRVAVKKLSR57 PFQSIIHAKR 67 TYRELRLLKH77 MKHENVIGLL87 DVFTPARSLE97 EFNDVYLVTH107 LMGADLNTDD 125 HVQFLIYQIL135 RGLKYIHSAD145 IIHRDLKPSN155 LAVNEDCELK165 ILDFYVATRW 187 YRAPEIMLNW197 MHYNQTVDIW207 SVGCIMAELL217 TGRTLFPGTD227 HIDQLKLILR 237 LVGTPGAELL247 KKISSESARN257 YIQSLTQMPK267 MNFANVFIGA277 NPLAVDLLEK 287 MLVLDSDKRI297 TAAQALAHAY307 FAQYHDPDDE317 PVADPYDQSF327 ESRDLLIDEW 337 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 .I46 or .I462 or .I463 or :3I46;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: 2YIW triazolopyridine inhibitors of p38 kinase | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGS37 VCAAFDTKTG47 LRVAVKKLSR57 PFQSIIHAKR 67 TYRELRLLKH77 MKHENVIGLL87 DVFTPARSLE97 EFNDVYLVTH107 LMGADLNTDD 125 HVQFLIYQIL135 RGLKYIHSAD145 IIHRDLKPSN155 LAVNEDCELK165 ILDFYVATRW 187 YRAPEIMLNW197 MHYNQTVDIW207 SVGCIMAELL217 TGRTLFPGTD227 HIDQLKLILR 237 LVGTPGAELL247 KKISSESARN257 YIQSLTQMPK267 MNFANVFIGA277 NPLAVDLLEK 287 MLVLDSDKRI297 TAAQALAHAY307 FAQYHDPDDE317 PVADPYDQSF327 ESRDLLIDEW 337 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 .I46 or .I462 or .I463 or :3I46;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: 6QDZ P38 alpha complex with AR117045 | ||||||
| Method | X-ray diffraction | Resolution | 1.73 Å | Mutation | No | [4] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGS37 VCAAFDTKTG47 LRVAVKKLSR57 PFQSIIHAKR 67 TYRELRLLKH77 MKHENVIGLL87 DVFTPARSLE97 EFNDVYLVTH107 LMGADLNNIL 122 TDDHVQFLIY132 QILRGLKYIH142 SADIIHRDLK152 PSNLAVNEDC162 ELKILDFGAT 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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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .I46 or .I462 or .I463 or :3I46;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: 6QE1 P38 alpha complex with AR117046 | ||||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [5] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGGSV38 CAAFDTKTGL48 RVAVKKLSRP58 FQSIIHAKRT 68 YRELRLLKHM78 KHENVIGLLD88 VFTPARSLEE98 FNDVYLVTHL108 MGADLNNIVK 118 LTDDHVQFLI131 YQILRGLKYI141 HSADIIHRDL151 KPSNLAVNED161 CELKILDFGA 184 TRWYRAPEIM194 LNWMHYNQTV204 DIWSVGCIMA214 ELLTGRTLFP224 GTDHIDQLKL 234 ILRLVGTPGA244 ELLKKISSES254 ARNYIQSLTQ264 MPKMNFANVF274 IGANPLAVDL 284 LEKMLVLDSD294 KRITAAQALA304 HAYFAQYHDP314 DDEPVADPYD324 QSFESRDLLI 334 DEWKSLTYDE344 VISFVPPP
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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 .I46 or .I462 or .I463 or :3I46;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: 3K3J P38alpha bound to novel DFG-out compound PF-00416121 | ||||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [6] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGG36 SVCAAFDTKT46 GLRVAVKKLS56 RPFQSIIHAK 66 RTYRELRLLK76 HMKHENVIGL86 LDVFTPARSL96 EEFNDVYLVT106 HLMGADLNNI 116 KLTDDHVQFL130 IYQILRGLKY140 IHSADIIHRD150 LKPSNLAVNE160 DCELKILDFV 183 ATRWYRAPEI193 MLNWMHYNQT203 VDIWSVGCIM213 AELLTGRTLF223 PGTDHIDQLK 233 LILRLVGTPG243 AELLKKISSE253 SARNYIQSLT263 QMPKMNFANV273 FIGANPLAVD 283 LLEKMLVLDS293 DKRITAAQAL303 AHAYFAQYHD313 PDDEPVADPY323 DQSFESRDLL 333 IDEWKSLTYD343 EVISFVPPP
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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 .I46 or .I462 or .I463 or :3I46;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: 3K3I p38alpha bound to novel DGF-out compound PF-00215955 | ||||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [6] |
| PDB Sequence |
RPTFYRQELN
14 KTIWEVPERY24 QNLSPVGSGA34 YGSVCAAFDT44 KTGLRVAVKK54 LSRPFQSIIH 64 AKRTYRELRL74 LKHMKHENVI84 GLLDVFTPAR94 SLEEFNDVYL104 VTHLMGADLN 114 NIKLTDDHVQ128 FLIYQILRGL138 KYIHSADIIH148 RDLKPSNLAV158 NEDCELKILD 168 FGVATRWYRA190 PEIMLNWMHY200 NQTVDIWSVG210 CIMAELLTGR220 TLFPGTDHID 230 QLKLILRLVG240 TPGAELLKKI250 SSESARNYIQ260 SLTQMPKMNF270 ANVFIGANPL 280 AVDLLEKMLV290 LDSDKRITAA300 QALAHAYFAQ310 YHDPDDEPVA320 DPYDQSFESR 330 DLLIDEWKSL340 TYDEVISFVP350 PP
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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 .I46 or .I462 or .I463 or :3I46;style chemicals stick;color identity;select .A:22 or .A:23 or .A:25 or .A:44 or .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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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural bioinformatics-based prediction of exceptional selectivity of p38 MAP kinase inhibitor PH-797804. Biochemistry. 2009 Jul 14;48(27):6402-11. | ||||
| REF 2 | Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5851-6. | ||||
| REF 3 | Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease. J Med Chem. 2011 Nov 24;54(22):7797-814. | ||||
| REF 4 | P38 alpha complex with AR117045 | ||||
| REF 5 | P38 alpha complex with AR117045 and AR117046 | ||||
| REF 6 | The design, synthesis and potential utility of fluorescence probes that target DFG-out conformation of p38alpha for high throughput screening binding assay. Chem Biol Drug Des. 2009 Dec;74(6):547-59. | ||||
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