Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T10822 | Target Info | |||
| Target Name | Cyclin-dependent kinase 8 (CDK8) | ||||
| Synonyms | Protein kinase K35; Mediator of RNA polymerase II transcription subunit CDK8; Mediator complex subunit CDK8; Cell division protein kinase 8 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | CDK8 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Sorafenib | Ligand Info | |||||
| Structure Description | Crystal Structure of human CDK8/CycC | PDB:3RGF | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [1] |
| PDB Sequence |
DKMDYDFKVK
8 LSSERERVED18 LFEYEGCKVG33 HVYKAKRKDG43 KDDKDYALKQ53 IEGTGISMSA 63 CREIALLREL73 KHPNVISLQK83 VFLSHADRKV93 WLLFDYAEHD103 LWHIIKFHRA 113 SKLPRGMVKS130 LLYQILDGIH140 YLHANWVLHR150 DLKPANILVM160 GEGPERGRVK 170 IADMGFARVT196 FWYRAPELLL206 GARHYTKAID216 IWAIGCIFAE226 LLTSEPIFHC 236 RQNPYHHDQL252 DRIFNVMGFP262 ADKDWEDIKK272 MPEHSTLMKD282 FRRNTYTNCS 292 LIKYMEKHKV302 KPDSKAFHLL312 QKLLTMDPIK322 RITSEQAMQD332 PYFLEDPLPT 342 SDVFAGCQIP352 Y
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VAL35
3.812
ALA50
3.335
LYS52
3.562
GLU66
2.761
LEU69
4.276
LEU70
3.682
LEU73
3.612
VAL78
3.459
ILE79
3.514
LEU95
4.871
PHE97
3.496
ASP98
3.555
TYR99
3.548
ALA100
2.647
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| Ligand Name: CCT251545 | Ligand Info | |||||
| Structure Description | CDK8/CYCC IN COMPLEX WITH 8-{3-Chloro-5-[4-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyridin- 4-yl}-2,8-diaza-spiro[4.5]decan-1-one | PDB:5BNJ | ||||
| Method | X-ray diffraction | Resolution | 2.64 Å | Mutation | No | [2] |
| PDB Sequence |
DKMDYDFKVK
8 LSSERERVED18 LFEYEGCKVG28 RGTYGHVYKA38 KRKDGKDDKD48 YALKQIEGTG 58 ISMSACREIA68 LLRELKHPNV78 ISLQKVFLSH88 ADRKVWLLFD98 YAEHDLWHII 108 KFHRASKANQ122 LPRGMVKSLL132 YQILDGIHYL142 HANWVLHRDL152 KPANILVMGE 162 GPERGRVKIA172 DMGFARLFNS182 PLTFWYRAPE203 LLLGARHYTK213 AIDIWAIGCI 223 FAELLTSEPI233 FHCRQNPYHH249 DQLDRIFNVM259 GFPADKDWED269 IKKMPEHSTL 279 MKDFRRNTYT289 NCSLIKYMEK299 HKVKPDSKAF309 HLLQKLLTMD319 PIKRITSEQA 329 MQDPYFLEDP339 LPTSDVFAGC349 QIPYPKREFL359 TEE
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| Ligand Name: N-[(4-chlorophenyl)methyl]quinazolin-4-amine | Ligand Info | |||||
| Structure Description | CDK8/Cyclin C in complex with N-(4-chlorobenzyl)isoquinolin-4-amine | PDB:6T41 | ||||
| Method | X-ray diffraction | Resolution | 2.45 Å | Mutation | No | [3] |
| PDB Sequence |
DDKMDYDFKV
7 KLSSERERVE17 DLFEYEGCKV27 GRGTYGHVYK37 AKRKDGKDDK47 DYALKQIEGT 57 GISMSACREI67 ALLRELKHPN77 VISLQKVFLS87 HADRKVWLLF97 DYAEHDLWHI 107 IKFHRASKAN117 PVQLPRGMVK129 SLLYQILDGI139 HYLHANWVLH149 RDLKPANILV 159 MGEGPERGRV169 KIADMGFARL179 FNSPLKPTFW198 YRAPELLLGA208 RHYTKAIDIW 218 AIGCIFAELL228 TSEPIFHCRQ238 ENPYHHDQLD253 RIFNVMGFPA263 DKDWEDIKKM 273 PEHSTLMKDF283 RRNTYTNCSL293 IKYMEKHKVK303 PDSKAFHLLQ313 KLLTMDPIKR 323 ITSEQAMQDP333 YFLEDPLPTS343 DVFAGCQIPY353 PKREFL
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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 .MFE or .MFE2 or .MFE3 or :3MFE;style chemicals stick;color identity;select .A:27 or .A:28 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:101 or .A:103 or .A:105 or .A:106 or .A:155 or .A:156 or .A:158 or .A:172 or .A:173 or .A:356 or .A:359; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL27
2.484
GLY28
2.822
VAL35
2.825
ALA50
2.862
LYS52
3.994
ILE79
2.205
PHE97
2.786
ASP98
2.830
TYR99
3.138
ALA100
2.118
GLU101
4.363
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| Ligand Name: 6-[5-chloranyl-4-[(1~{S})-1-oxidanylethyl]pyridin-3-yl]-3,4-dihydro-2~{H}-1,8-naphthyridine-1-carboxamide | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF CDK8-CycC IN COMPLEX WITH COMPOUND 1 | PDB:6R3S | ||||
| Method | X-ray diffraction | Resolution | 2.19 Å | Mutation | No | [4] |
| PDB Sequence |
DDKMDYDFKV
7 KLSSERERVE17 DLFEYEGCKV27 GRGHVYKAKR40 KDGKDDKDYA50 LKQIEGTGIS 60 MSACREIALL70 RELKHPNVIS80 LQKVFLSHAD90 RKVWLLFDYA100 EHDLWHIIKF 110 HRASKANKQL123 PRGMVKSLLY133 QILDGIHYLH143 ANWVLHRDLK153 PANILVMGEG 163 PERGRVKIAD173 MGFARLFNSP183 LKPTFWYRAP202 ELLLGARHYT212 KAIDIWAIGC 222 IFAELLTSEP232 IFHCRQTSNP246 YHHDQLDRIF256 NVMGFPADKD266 WEDIKKMPEH 276 STLMKDFRRN286 TYTNCSLIKY296 MEKHKVKPDS306 KAFHLLQKLL316 TMDPIKRITS 326 EQAMQDPYFL336 EDPLPTSDVF346 AGCQIPYPKR356 EFLTEE
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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 .JRE or .JRE2 or .JRE3 or :3JRE;style chemicals stick;color identity;select .A:27 or .A:28 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:106 or .A:155 or .A:158 or .A:172 or .A:173 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 4-(4-Iodophenoxy)-N-Methylthieno[2,3-C]pyridine-2-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of CDK8:Cyclin C complex with compound 22 | PDB:5CEI | ||||
| Method | X-ray diffraction | Resolution | 2.24 Å | Mutation | No | [5] |
| PDB Sequence |
KMDYDFKVKL
9 SSERERVEDL19 FEYEGCKVGR29 GTYGHVYKAK39 RKDGKDDKDY49 ALKQIEGTGI 59 SMSACREIAL69 LRELKHPNVI79 SLQKVFLSHA89 DRKVWLLFDY99 AEHDLWHIIK 109 FHRASKAQLP124 RGMVKSLLYQ134 ILDGIHYLHA144 NWVLHRDLKP154 ANILVMGEGP 164 ERGRVKIADM174 GFARLFNSPL184 KPTFWYRAPE203 LLLGARHYTK213 AIDIWAIGCI 223 FAELLTSEPI233 FHCRQESNPY247 HHDQLDRIFN257 VMGFPADKDW267 EDIKKMPEHS 277 TLMKDFRRNT287 YTNCSLIKYM297 EKHKVKPDSK307 AFHLLQKLLT317 MDPIKRITSE 327 QAMQDPYFLE337 DPLPTSDVFA347 GCQIPYPKRE357 FLTEE
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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 .50R or .50R2 or .50R3 or :350R;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:105 or .A:106 or .A:155 or .A:158 or .A:172 or .A:173 or .A:356; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-{(3s)-1-[2-(Methylamino)pyrimidin-4-Yl]pyrrolidin-3-Yl}-N'-{4-[(Morpholin-4-Yl)methyl]-3-(Trifluoromethyl)phenyl}urea | Ligand Info | |||||
| Structure Description | CDK8/CYCC IN COMPLEX WITH COMPOUND 20 | PDB:5HVY | ||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | No | [6] |
| PDB Sequence |
DKMDYDFKVK
8 LSSERERVED18 LFEYEGCKVG28 GHVYKAKRKD42 GKDDKDYALK52 QIEGTGISMS 62 ACREIALLRE72 LKHPNVISLQ82 KVFLSHADRK92 VWLLFDYAEH102 DLWHIIKFHR 112 ASVQLPRGMV128 KSLLYQILDG138 IHYLHANWVL148 HRDLKPANIL158 VMGEGPERGR 168 VKIADMGFAR178 LPVVVTFWYR200 APELLLGARH210 YTKAIDIWAI220 GCIFAELLTS 230 EPIFHCRKTS244 NPYHHDQLDR254 IFNVMGFPAD264 KDWEDIKKMP274 EHSTLMKDFR 284 RNTYTNCSLI294 KYMEKHKVKP304 DSKAFHLLQK314 LLTMDPIKRI324 TSEQAMQDPY 334 FLEDPLPTSD344 VFAGCQIPYP354 KREFL
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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 .66X or .66X2 or .66X3 or :366X;style chemicals stick;color identity;select .A:27 or .A:35 or .A:36 or .A:50 or .A:52 or .A:65 or .A:66 or .A:69 or .A:70 or .A:73 or .A:78 or .A:79 or .A:95 or .A:97 or .A:98 or .A:99 or .A:100 or .A:142 or .A:147 or .A:148 or .A:149 or .A:150 or .A:158 or .A:171 or .A:172 or .A:173 or .A:174 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL27
2.682
VAL35
2.305
TYR36
4.915
ALA50
2.999
LYS52
2.839
ARG65
3.904
GLU66
2.449
LEU69
1.985
LEU70
2.847
LEU73
3.570
VAL78
3.083
ILE79
2.220
LEU95
4.826
PHE97
2.756
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| Ligand Name: cortistatin A | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8-Cyclin C in complex with cortistatin A | PDB:4CRL | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [7] |
| PDB Sequence |
DDKMDYDFKV
7 KLSSERERVE17 DLFEYEGCKV27 GRGTYGHVYK37 AKRKDGKDDK47 DYALKQIEGT 57 GISMSACREI67 ALLRELKHPN77 VISLQKVFLS87 HADRKVWLLF97 DYAEHDLWHI 107 IKFHRASVQL123 PRGMVKSLLY133 QILDGIHYLH143 ANWVLHRDLK153 PANILVMGEG 163 PERGRVKIAD173 MGFARLFNSP183 LVTFWYRAPE203 LLLGARHYTK213 AIDIWAIGCI 223 FAELLTSEPI233 FHCRQPYHHD250 QLDRIFNVMG260 FPADKDWEDI270 KKMPEHSTLM 280 KDFRRNTYTN290 CSLIKYMEKH300 KVKPDSKAFH310 LLQKLLTMDP320 IKRITSEQAM 330 QDPYFLEDPL340 PTSDVFAGCQ350 IPYPKREFL
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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 .C1I or .C1I2 or .C1I3 or :3C1I;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:105 or .A:106 or .A:153 or .A:155 or .A:156 or .A:158 or .A:356; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 1-[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]-3-[3-(Morpholin-4-Yl)propyl]urea | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in complex with compound 5 (1-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-3-[3-(morpholin-4-yl)propyl]urea) | PDB:4F6U | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [8] |
| PDB Sequence |
DKMDYDFKVK
8 LSSERERVED18 LFEYEGCKVG28 RGTYGHVYKA38 KRKDGKDDKD48 YALKQIEGTG 58 ISMSACREIA68 LLRELKHPNV78 ISLQKVFLSH88 ADRKVWLLFD98 YAEHDLWHII 108 KFHRASKVQL123 PRGMVKSLLY133 QILDGIHYLH143 ANWVLHRDLK153 PANILVMGEG 163 PERGRVKIAD173 MGFVVTFWYR200 APELLLGARH210 YTKAIDIWAI220 GCIFAELLTS 230 EPIFHCRQEN245 PYHHDQLDRI255 FNVMGFPADK265 DWEDIKKMPE275 HSTLMKDFRR 285 NTYTNCSLIK295 YMEKHKVKPD305 SKAFHLLQKL315 LTMDPIKRIT325 SEQAMQDPYF 335 LEDPLPTSDV345 FAGCQIPYPK355 REFL
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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 .0SR or .0SR2 or .0SR3 or :30SR;style chemicals stick;color identity;select .A:32 or .A:35 or .A:50 or .A:52 or .A:62 or .A:65 or .A:66 or .A:70 or .A:73 or .A:78 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:142 or .A:147 or .A:149 or .A:158 or .A:171 or .A:172 or .A:173 or .A:174 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TYR32
3.680
VAL35
3.957
ALA50
3.526
LYS52
3.854
SER62
3.330
ARG65
3.580
GLU66
2.747
LEU70
3.922
LEU73
3.638
VAL78
3.925
ILE79
3.536
PHE97
3.655
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| Ligand Name: N-(2-phenylethyl)quinazolin-4-amine | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in the DMG-in conformation | PDB:4F7S | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [8] |
| PDB Sequence |
MDYDFKVKLS
10 SERERVEDLF20 EYEGCKVGRG30 TYGHVYKAKR40 KDGKDDKDYA50 LKQIEGTGIS 60 MSACREIALL70 RELKHPNVIS80 LQKVFLSHAD90 RKVWLLFDYA100 EHDLWHIIKF 110 HRASKQLPRG126 MVKSLLYQIL136 DGIHYLHANW146 VLHRDLKPAN156 ILVMGEGPER 166 GRVKIADMGF176 ARLFNSPLKP186 TFWYRAPELL205 LGARHYTKAI215 DIWAIGCIFA 225 ELLTSEPIFH235 CRTSNPYHHD250 QLDRIFNVMG260 FPADKDWEDI270 KKMPEHSTLM 280 KDFRRNTYTN290 CSLIKYMEKH300 KVKPDSKAFH310 LLQKLLTMDP320 IKRITSEQAM 330 QDPYFLEDPL340 PTSDVFAGCQ350 IPYPKREFL
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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 .0SW or .0SW2 or .0SW3 or :30SW;style chemicals stick;color identity;select .A:27 or .A:28 or .A:35 or .A:50 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:105 or .A:106 or .A:155 or .A:158 or .A:172 or .A:173 or .A:356; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: N-[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]-4-[2-({[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]carbamoyl}amino)ethyl]piperazine-1-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in complex with compound 1 (N-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-4-[2-({[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]carbamoyl}amino)ethyl]piperazine-1-carboxamide) | PDB:4F6W | ||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | No | [8] |
| PDB Sequence |
MDYDFKVKLS
10 SERERVEDLF20 EYEGCKVGRG30 TYGHVYKAKR40 KDGKDDKDYA50 LKQIEGTGIS 60 MSACREIALL70 RELKHPNVIS80 LQKVFLSHAD90 RKVWLLFDYA100 EHDLWHIIKF 110 HRASKVQLPR125 GMVKSLLYQI135 LDGIHYLHAN145 WVLHRDLKPA155 NILVMGEGPE 165 RGRVKIADMG175 FATFWYRAPE203 LLLGARHYTK213 AIDIWAIGCI223 FAELLTSEPI 233 FHCRQNPYHH249 DQLDRIFNVM259 GFPADKDWED269 IKKMPEHSTL279 MKDFRRNTYT 289 NCSLIKYMEK299 HKVKPDSKAF309 HLLQKLLTMD319 PIKRITSEQA329 MQDPYFLEDP 339 LPTSDVFAGC349 QIPYPKREFL359
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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 .0SS or .0SS2 or .0SS3 or :30SS;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:62 or .A:65 or .A:66 or .A:69 or .A:70 or .A:73 or .A:78 or .A:79 or .A:97 or .A:99 or .A:100 or .A:103 or .A:105 or .A:106 or .A:142 or .A:147 or .A:148 or .A:149 or .A:155 or .A:156 or .A:158 or .A:171 or .A:172 or .A:173 or .A:174 or .A:175 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL27
3.605
GLY28
4.619
TYR32
3.232
VAL35
3.817
ALA50
4.289
LYS52
4.068
SER62
3.306
ARG65
4.200
GLU66
2.840
LEU69
4.470
LEU70
3.884
LEU73
3.729
VAL78
3.820
ILE79
3.150
PHE97
3.654
TYR99
3.711
ALA100
4.226
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| Ligand Name: US11213520, Example I-015 | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in complex with BI 919811 | PDB:6QTJ | ||||
| Method | X-ray diffraction | Resolution | 2.48 Å | Mutation | No | [4] |
| PDB Sequence |
SMDYDFKVKL
9 SSERERVEDL19 FEYEGCKVGR29 GTYGHVYKAK39 RKDGKDDKDY49 ALKQIEGTGI 59 SMSACREIAL69 LRELKHPNVI79 SLQKVFLSHA89 DRKVWLLFDY99 AEHDLWHIIK 109 FHRASKLPRG126 MVKSLLYQIL136 DGIHYLHANW146 VLHRDLKPAN156 ILVMGEGPER 166 GRVKIADMGF176 VTFWYRAPEL204 LLGARHYTKA214 IDIWAIGCIF224 AELLTSEPIF 234 HCRQSNPYHH249 DQLDRIFNVM259 GFPADKDWED269 IKKMPEHSTL279 MKDFRRNTYT 289 NCSLIKYMEK299 HKVKPDSKAF309 HLLQKLLTMD319 PIKRITSEQA329 MQDPYFLEDP 339 LPTSDVFAGC349 QIPYPKREFL359
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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 .JHK or .JHK2 or .JHK3 or :3JHK;style chemicals stick;color identity;select .A:27 or .A:28 or .A:29 or .A:32 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:105 or .A:106 or .A:155 or .A:158 or .A:172 or .A:173 or .A:356 or .A:359; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL27
3.247
GLY28
3.571
ARG29
3.038
TYR32
4.271
VAL35
3.669
ALA50
3.283
LYS52
4.545
ILE79
3.835
PHE97
3.464
ASP98
3.516
TYR99
3.771
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| Ligand Name: 1-[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]-3-(2-Hydroxyethyl)urea | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in complex with compound 3 (1-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-3-(2-hydroxyethyl)urea) | PDB:4F7J | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [8] |
| PDB Sequence |
MDYDFKVKLS
10 SERERVEDLF20 EYEGCKVGRG30 TYGHVYKAKR40 KDGKDDKDYA50 LKQIEGTGIS 60 MSACREIALL70 RELKHPNVIS80 LQKVFLSHAD90 RKVWLLFDYA100 EHDLWHIIKF 110 HRQLPRGMVK129 SLLYQILDGI139 HYLHANWVLH149 RDLKPANILV159 MGEGPERGRV 169 KIADMGFVTF197 WYRAPELLLG207 ARHYTKAIDI217 WAIGCIFAEL227 LTSEPIFHCR 237 QNPYHHDQLD253 RIFNVMGFPA263 DKDWEDIKKM273 PEHSTLMKDF283 RRNTYTNCSL 293 IKYMEKHKVK303 PDSKAFHLLQ313 KLLTMDPIKR323 ITSEQAMQDP333 YFLEDPLPTS 343 DVFAGCQIPY353 PKREFL
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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 .0SU or .0SU2 or .0SU3 or :30SU;style chemicals stick;color identity;select .A:32 or .A:35 or .A:52 or .A:62 or .A:63 or .A:65 or .A:66 or .A:69 or .A:70 or .A:73 or .A:78 or .A:79 or .A:97 or .A:142 or .A:147 or .A:148 or .A:149 or .A:171 or .A:172 or .A:173 or .A:174; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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TYR32
3.827
VAL35
4.235
LYS52
3.097
SER62
3.122
ALA63
4.994
ARG65
3.341
GLU66
2.958
LEU69
4.542
LEU70
3.842
LEU73
4.001
VAL78
3.621
|
|||||
| Ligand Name: 1-[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]urea | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in complex with compound 7 (1-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]urea) | PDB:4F6S | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [8] |
| PDB Sequence |
KMDYDFKVKL
9 SSERERVEDL19 FEYEGCKVGR29 GTYGHVYKAK39 RKDGKDDKDY49 ALKQIEGTGI 59 SMSACREIAL69 LRELKHPNVI79 SLQKVFLSHA89 DRKVWLLFDY99 AEHDLWHIIK 109 FHRASLPRGM127 VKSLLYQILD137 GIHYLHANWV147 LHRDLKPANI157 LVMGEGPERG 167 RVKIADMGFA177 VTFWYRAPEL204 LLGARHYTKA214 IDIWAIGCIF224 AELLTSEPIF 234 HCRNPYHHDQ251 LDRIFNVMGF261 PADKDWEDIK271 KMPEHSTLMK281 DFRRNTYTNC 291 SLIKYMEKHK301 VKPDSKAFHL311 LQKLLTMDPI321 KRITSEQAMQ331 DPYFLEDPLP 341 TSDVFAGCQI351 PYPKREFL
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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 .0SQ or .0SQ2 or .0SQ3 or :30SQ;style chemicals stick;color identity;select .A:32 or .A:52 or .A:62 or .A:63 or .A:65 or .A:66 or .A:70 or .A:73 or .A:78 or .A:79 or .A:97 or .A:142 or .A:147 or .A:148 or .A:149 or .A:171 or .A:172 or .A:173 or .A:174; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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||||||
| Ligand Name: 1-[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]-3-(5-Hydroxypentyl)urea | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in complex with compound 11 (1-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-3-(5-hydroxypentyl)urea) | PDB:4F7N | ||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [8] |
| PDB Sequence |
KMDYDFKVKL
9 SSERERVEDL19 FEYEGCKVGR29 GTYGHVYKAK39 RKDGKDDKDY49 ALKQIEGTGI 59 SMSACREIAL69 LRELKHPNVI79 SLQKVFLSHA89 DRKVWLLFDY99 AEHDLWHIIK 109 FHRASVQLPR125 GMVKSLLYQI135 LDGIHYLHAN145 WVLHRDLKPA155 NILVMGEGPE 165 RGRVKIADMG175 FVVTFWYRAP202 ELLLGARHYT212 KAIDIWAIGC222 IFAELLTSEP 232 IFHCRQENPY247 HHDQLDRIFN257 VMGFPADKDW267 EDIKKMPEHS277 TLMKDFRRNT 287 YTNCSLIKYM297 EKHKVKPDSK307 AFHLLQKLLT317 MDPIKRITSE327 QAMQDPYFLE 337 DPLPTSDVFA347 GCQIPYPKRE357 FLTE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .0SV or .0SV2 or .0SV3 or :30SV;style chemicals stick;color identity;select .A:32 or .A:35 or .A:50 or .A:52 or .A:62 or .A:65 or .A:66 or .A:70 or .A:73 or .A:78 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:142 or .A:147 or .A:148 or .A:149 or .A:158 or .A:171 or .A:172 or .A:173 or .A:174; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR32
3.771
VAL35
4.623
ALA50
3.316
LYS52
3.885
SER62
3.357
ARG65
3.464
GLU66
3.334
LEU70
3.785
LEU73
3.544
VAL78
3.963
ILE79
3.318
PHE97
3.724
|
|||||
| Ligand Name: 2-(4-(4-(isoquinolin-4-yl)phenyl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in complex with BI-1347 | PDB:6QTG | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [4] |
| PDB Sequence |
SMDYDFKVKL
9 SSERERVEDL19 FEYEGCKVGR29 GTYGHVYKAK39 RKDGKDDKDY49 ALKQIEGTGI 59 SMSACREIAL69 LRELKHPNVI79 SLQKVFLSHA89 DRKVWLLFDY99 AEHDLWHIIK 109 FHRASKLPRG126 MVKSLLYQIL136 DGIHYLHANW146 VLHRDLKPAN156 ILVMGEGPER 166 GRVKIADMGV195 TFWYRAPELL205 LGARHYTKAI215 DIWAIGCIFA225 ELLTSEPIFH 235 CRQSNPYHHD250 QLDRIFNVMG260 FPADKDWEDI270 KKMPEHSTLM280 KDFRRNTYTN 290 CSLIKYMEKH300 KVKPDSKAFH310 LLQKLLTMDP320 IKRITSEQAM330 QDPYFLEDPL 340 PTSDVFAGCQ350 IPYPKREFL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .JH8 or .JH82 or .JH83 or :3JH8;style chemicals stick;color identity;select .A:27 or .A:28 or .A:29 or .A:32 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:105 or .A:106 or .A:155 or .A:158 or .A:172 or .A:173 or .A:356 or .A:359; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL27
3.239
GLY28
3.568
ARG29
3.171
TYR32
4.571
VAL35
3.731
ALA50
3.336
LYS52
4.424
ILE79
3.895
PHE97
3.508
ASP98
3.520
TYR99
3.815
|
|||||
| Ligand Name: (R)-butane-1,2-diol | Ligand Info | |||||
| Structure Description | CDK8/CyclinC in complex with drug ETP-50775 | PDB:6TPA | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [9] |
| PDB Sequence |
SKMDYDFKVK
8 LSSERERVED18 LFEYEGCKVG28 RGTYGHVYKA38 KRKDGKDDKD48 YALKQIEGTG 58 ISMSACREIA68 LLRELKHPNV78 ISLQKVFLSH88 ADRKVWLLFD98 YAEHDLWHII 108 KFHRASKKPV121 QLPRGMVKSL131 LYQILDGIHY141 LHANWVLHRD151 LKPANILVMG 161 EGPERGRVKI171 ADMGFARLTF197 WYRAPELLLG207 ARHYTKAIDI217 WAIGCIFAEL 227 LTSEPIFHCR237 QNPYHHDQLD253 RIFNVMGFPA263 DKDWEDIKKM273 PEHSTLMKDF 283 RRNTYTNCSL293 IKYMEKHKVK303 PDSKAFHLLQ313 KLLTMDPIKR323 ITSEQAMQDP 333 YFLEDPLPTS343 DVFAGCQIPY353 PKREFL
|
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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 .NZ5 or .NZ52 or .NZ53 or :3NZ5;style chemicals stick;color identity;select .A:71 or .A:81 or .A:82 or .A:83 or .A:125 or .A:126 or .A:129 or .A:133 or .A:306 or .A:307 or .A:308 or .A:334 or .A:337 or .A:338 or .A:339 or .A:341 or .A:342 or .A:343; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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||||||
| Ligand Name: Cdk8-IN-10 | Ligand Info | |||||
| Structure Description | CDK8/CyclinC in complex with drug ETP-50775 | PDB:6TPA | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [9] |
| PDB Sequence |
SKMDYDFKVK
8 LSSERERVED18 LFEYEGCKVG28 RGTYGHVYKA38 KRKDGKDDKD48 YALKQIEGTG 58 ISMSACREIA68 LLRELKHPNV78 ISLQKVFLSH88 ADRKVWLLFD98 YAEHDLWHII 108 KFHRASKKPV121 QLPRGMVKSL131 LYQILDGIHY141 LHANWVLHRD151 LKPANILVMG 161 EGPERGRVKI171 ADMGFARLTF197 WYRAPELLLG207 ARHYTKAIDI217 WAIGCIFAEL 227 LTSEPIFHCR237 QNPYHHDQLD253 RIFNVMGFPA263 DKDWEDIKKM273 PEHSTLMKDF 283 RRNTYTNCSL293 IKYMEKHKVK303 PDSKAFHLLQ313 KLLTMDPIKR323 ITSEQAMQDP 333 YFLEDPLPTS343 DVFAGCQIPY353 PKREFL
|
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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 .NZ8 or .NZ82 or .NZ83 or :3NZ8;style chemicals stick;color identity;select .A:32 or .A:35 or .A:50 or .A:52 or .A:66 or .A:69 or .A:70 or .A:73 or .A:78 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:142 or .A:147 or .A:148 or .A:149 or .A:158 or .A:171 or .A:172 or .A:173 or .A:174 or .A:176 or .A:356; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR32
3.383
VAL35
3.541
ALA50
3.609
LYS52
3.182
GLU66
2.724
LEU69
4.220
LEU70
3.431
LEU73
3.660
VAL78
3.337
ILE79
3.487
PHE97
3.547
ASP98
3.662
TYR99
3.871
|
|||||
| Ligand Name: Tert-Butyl [3-({[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]carbamoyl}amino)propyl]carbamate | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in complex with compound 2 (tert-butyl [3-({[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]carbamoyl}amino)propyl]carbamate) | PDB:4F7L | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [8] |
| PDB Sequence |
DKMDYDFKVK
8 LSSERERVED18 LFEYEGCKVG28 RGTYGHVYKA38 KRKDGKDDKD48 YALKQIEGTG 58 ISMSACREIA68 LLRELKHPNV78 ISLQKVFLSH88 ADRKVWLLFD98 YAEHDLWHII 108 KFHRASQLPR125 GMVKSLLYQI135 LDGIHYLHAN145 WVLHRDLKPA155 NILVMGEGPE 165 RGRVKIADMG175 TFWYRAPELL205 LGARHYTKAI215 DIWAIGCIFA225 ELLTSEPIFH 235 CRQNPYHHDQ251 LDRIFNVMGF261 PADKDWEDIK271 KMPEHSTLMK281 DFRRNTYTNC 291 SLIKYMEKHK301 VKPDSKAFHL311 LQKLLTMDPI321 KRITSEQAMQ331 DPYFLEDPLP 341 TSDVFAGCQI351 PYPKREFL
|
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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 .0SO or .0SO2 or .0SO3 or :30SO;style chemicals stick;color identity;select .A:27 or .A:32 or .A:35 or .A:50 or .A:52 or .A:62 or .A:65 or .A:66 or .A:70 or .A:73 or .A:78 or .A:79 or .A:97 or .A:99 or .A:100 or .A:142 or .A:147 or .A:149 or .A:158 or .A:171 or .A:172 or .A:173 or .A:174 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
VAL27
3.854
TYR32
3.387
VAL35
3.547
ALA50
3.568
LYS52
3.662
SER62
3.224
ARG65
3.851
GLU66
3.015
LEU70
3.893
LEU73
3.951
VAL78
4.137
ILE79
3.093
|
|||||
| Ligand Name: 1-[3-Tert-Butyl-1-(4-Methylphenyl)-1h-Pyrazol-5-Yl]-3-[2-(Morpholin-4-Yl)ethyl]urea | Ligand Info | |||||
| Structure Description | Crystal structure of human CDK8/CYCC in complex with compound 4 (1-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-3-[2-(morpholin-4-yl)ethyl]urea) | PDB:4F70 | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [8] |
| PDB Sequence |
KMDYDFKVKL
9 SSERERVEDL19 FEYEGCKVGR29 GTYGHVYKAK39 RKDGKDDKDY49 ALKQIEGTGI 59 SMSACREIAL69 LRELKHPNVI79 SLQKVFLSHA89 DRKVWLLFDY99 AEHDLWHIIK 109 FHRASKALPR125 GMVKSLLYQI135 LDGIHYLHAN145 WVLHRDLKPA155 NILVMGEGPE 165 RGRVKIADMV195 TFWYRAPELL205 LGARHYTKAI215 DIWAIGCIFA225 ELLTSEPIFH 235 CRNPYHHDQL252 DRIFNVMGFP262 ADKDWEDIKK272 MPEHSTLMKD282 FRRNTYTNCS 292 LIKYMEKHKV302 KPDSKAFHLL312 QKLLTMDPIK322 RITSEQAMQD332 PYFLEDPLPT 342 SDVFAGCQIP352 YPKREFL
|
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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 .0ST or .0ST2 or .0ST3 or :30ST;style chemicals stick;color identity;select .A:32 or .A:35 or .A:52 or .A:62 or .A:63 or .A:65 or .A:66 or .A:70 or .A:73 or .A:78 or .A:79 or .A:97 or .A:142 or .A:147 or .A:148 or .A:149 or .A:155 or .A:156 or .A:158 or .A:171 or .A:172 or .A:173 or .A:174; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TYR32
4.510
VAL35
3.573
LYS52
3.783
SER62
3.351
ALA63
4.773
ARG65
3.451
GLU66
3.316
LEU70
3.868
LEU73
3.812
VAL78
4.057
ILE79
3.314
PHE97
3.719
|
|||||
| Ligand Name: 3-Chloranyl-4-Pyridin-4-Yl-1h-Pyrrole-2-Carboxamide | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH COMPOUND 17:3-chloro-4-(4-pyridyl)-1H-pyrrole-2-carboxamide | PDB:5XS2 | ||||
| Method | X-ray diffraction | Resolution | 2.04 Å | Mutation | No | [10] |
| PDB Sequence |
MEFMDYDFKV
7 KLSSERERVE17 DLFEYEGCKV27 GRGTYGHVYK37 AKRKDGKDDK47 DYALKQIEGT 57 GISMSACREI67 ALLRELKHPN77 VISLQKVFLS87 HADRKVWLLF97 DYAEHDLWHI 107 IKFHRASKAN117 KKPVQLPRGM127 VKSLLYQILD137 GIHYLHANWV147 LHRDLKPANI 157 LVMGEGPERG167 RVKIADMGFA177 RLFNSPLKPL187 ADLDPVVVTF197 WYRAPELLLG 207 ARHYTKAIDI217 WAIGCIFAEL227 LTSEPIFHCR237 QEDIKTSNPY247 HHDQLDRIFN 257 VMGFPADKDW267 EDIKKMPEHS277 TLMKDFRRNT287 YTNCSLIKYM297 EKHKVKPDSK 307 AFHLLQKLLT317 MDPIKRITSE327 QAMQDPYFLE337 DPLPTSDVFA347 GCQIPYPKRE 357 FLTEEE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .8D6 or .8D62 or .8D63 or :38D6;style chemicals stick;color identity;select .A:32 or .A:35 or .A:50 or .A:52 or .A:66 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:155 or .A:156 or .A:158 or .A:172 or .A:173 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: N-Methyl-4-Pyridin-4-Yl-1h-Pyrrole-2-Carboxamide | Ligand Info | |||||
| Structure Description | Human CDK8-CYCC in complex with compound 4: N-methyl-4-(4-pyridyl)-1H-pyrrole-2-carboxamide | PDB:5XQX | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [10] |
| PDB Sequence |
MEFMDYDFKV
7 KLSSERERVE17 DLFEYEGCKV27 GRGTYGHVYK37 AKRKDGKDDK47 DYALKQIEGT 57 GISMSACREI67 ALLRELKHPN77 VISLQKVFLS87 HADRKVWLLF97 DYAEHDLWHI 107 IKFHRASLPR125 GMVKSLLYQI135 LDGIHYLHAN145 WVLHRDLKPA155 NILVMGEGPE 165 RGRVKIADMG175 FARLFNVTFW198 YRAPELLLGA208 RHYTKAIDIW218 AIGCIFAELL 228 TSEPIFHCRQ238 ESNPYHHDQL252 DRIFNVMGFP262 ADKDWEDIKK272 MPEHSTLMKD 282 FRRNTYTNCS292 LIKYMEKHKV302 KPDSKAFHLL312 QKLLTMDPIK322 RITSEQAMQD 332 PYFLEDPLPT342 SDVFAGCQIP352 YPKREFLTEE362
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .8CC or .8CC2 or .8CC3 or :38CC;style chemicals stick;color identity;select .A:32 or .A:35 or .A:50 or .A:52 or .A:66 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:156 or .A:158 or .A:172 or .A:173 or .A:356; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: [(2s)-2-(4-Chlorophenyl)pyrrolidin-1-Yl](3-Methyl-1h-Pyrazolo[3,4-B]pyridin-5-Yl)methanone | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH [(S)-2-(4-Chloro-phenyl)-pyrrolidin-1-yl]-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-methanone | PDB:5IDN | ||||
| Method | X-ray diffraction | Resolution | 2.26 Å | Mutation | No | [11] |
| PDB Sequence |
MDYDFKVKLS
10 SERERVEDLF20 EYEGCKVGRG30 TYGHVYKAKR40 KDGKDDKDYA50 LKQIEGTGIS 60 MSACREIALL70 RELKHPNVIS80 LQKVFLSHAD90 RKVWLLFDYA100 EHDLWHIIKF 110 HRASKANLPR125 GMVKSLLYQI135 LDGIHYLHAN145 WVLHRDLKPA155 NILVMGEGPE 165 RGRVKIADMG175 FARVTFWYRA201 PELLLGARHY211 TKAIDIWAIG221 CIFAELLTSE 231 PIFHCRQNPY247 HHDQLDRIFN257 VMGFPADKDW267 EDIKKMPEHS277 TLMKDFRRNT 287 YTNCSLIKYM297 EKHKVKPDSK307 AFHLLQKLLT317 MDPIKRITSE327 QAMQDPYFLE 337 DPLPTSDVFA347 GCQIPYPKRE357 FLTEEE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .6A7 or .6A72 or .6A73 or :36A7;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:66 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:155 or .A:156 or .A:158 or .A:172 or .A:173 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: [6-Hydroxy-3-(3-Methylbenzyl)-1h-Indazol-5-Yl][(3s)-3-Hydroxypyrrolidin-1-Yl]methanone | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH [6-Hydroxy-3-(3-methyl-benzyl)-1H-indazol-5-yl]-((S)-3-hydroxy-pyrrolidin-1-yl)-methanone | PDB:5HNB | ||||
| Method | X-ray diffraction | Resolution | 2.35 Å | Mutation | No | [12] |
| PDB Sequence |
DDKMDYDFKV
7 KLSSERERVE17 DLFEYEGCKV27 GRGTYGHVYK37 AKRKDGKDDK47 DYALKQIEGT 57 GISMSACREI67 ALLRELKHPN77 VISLQKVFLS87 HADRKVWLLF97 DYAEHDLWHI 107 IKFHRASKAL123 PRGMVKSLLY133 QILDGIHYLH143 ANWVLHRDLK153 PANILVMGEG 163 PERGRVKIAD173 MGFARLFNSP183 LKTFWYRAPE203 LLLGARHYTK213 AIDIWAIGCI 223 FAELLTSEPI233 FHCRQESNPY247 HHDQLDRIFN257 VMGFPADKDW267 EDIKKMPEHS 277 TLMKDFRRNT287 YTNCSLIKYM297 EKHKVKPDSK307 AFHLLQKLLT317 MDPIKRITSE 327 QAMQDPYFLE337 DPLPTSDVFA347 GCQIPYPKRE357 FL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .62M or .62M2 or .62M3 or :362M;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:155 or .A:156 or .A:158 or .A:172 or .A:173 or .A:356; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: N-Methyl-8-(1-Methyl-2,2-Dioxo-2,3-Dihydro-1h-2lambda~6~,1-Benzothiazol-5-Yl)-1,6-Naphthyridine-2-Carboxamide | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH 8-(1-Methyl-2,2-dioxo-2,3-dihydro-1H-2l6-benzo[c]isothiazol-5-yl)-[1,6]naphthyridine-2-carboxylic acid methylamide | PDB:5I5Z | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [13] |
| PDB Sequence |
DDKMDYDFKV
7 KLSSERERVE17 DLFEYEGCKV27 GRGTYGHVYK37 AKRKDGKDDK47 DYALKQIEGT 57 GISMSACREI67 ALLRELKHPN77 VISLQKVFLS87 HADRKVWLLF97 DYAEHDLWHI 107 IKFHRASKAN117 LPRGMVKSLL132 YQILDGIHYL142 HANWVLHRDL152 KPANILVMGE 162 GPERGRVKIA172 DMGFARLFNS182 PLKTFWYRAP202 ELLLGARHYT212 KAIDIWAIGC 222 IFAELLTSEP232 IFHCRQSNPY247 HHDQLDRIFN257 VMGFPADKDW267 EDIKKMPEHS 277 TLMKDFRRNT287 YTNCSLIKYM297 EKHKVKPDSK307 AFHLLQKLLT317 MDPIKRITSE 327 QAMQDPYFLE337 DPLPTSDVFA347 GCQIPYPKRE357 FLTEE
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .68U or .68U2 or .68U3 or :368U;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:106 or .A:155 or .A:158 or .A:172 or .A:173 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: (3-Amino-1h-Indazol-5-Yl)[(2s)-2-(4-Fluorophenyl)piperidin-1-Yl]methanone | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH (3-Amino-1H-indazol-5-yl)-[(S)-2-(4-fluoro-phenyl)-piperidin-1-yl]-methanone | PDB:5IDP | ||||
| Method | X-ray diffraction | Resolution | 2.65 Å | Mutation | No | [11] |
| PDB Sequence |
KMDYDFKVKL
9 SSERERVEDL19 FEYEGCKVGR29 GTYGHVYKAK39 RKDGKDDKDY49 ALKQIEGTGI 59 SMSACREIAL69 LRELKHPNVI79 SLQKVFLSHA89 DRKVWLLFDY99 AEHDLWHIIK 109 FHRASKVQLP124 RGMVKSLLYQ134 ILDGIHYLHA144 NWVLHRDLKP154 ANILVMGEGP 164 ERGRVKIADM174 GFARLFNSPL184 KTFWYRAPEL204 LLGARHYTKA214 IDIWAIGCIF 224 AELLTSEPIF234 HCRQETSNPY247 HHDQLDRIFN257 VMGFPADKDW267 EDIKKMPEHS 277 TLMKDFRRNT287 YTNCSLIKYM297 EKHKVKPDSK307 AFHLLQKLLT317 MDPIKRITSE 327 QAMQDPYFLE337 DPLPTSDVFA347 GCQIPYPKRE357 FL
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .6A6 or .6A62 or .6A63 or :36A6;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:106 or .A:155 or .A:156 or .A:158 or .A:172 or .A:173 or .A:356; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| Ligand Name: [(2S)-2-(4-chlorophenyl)pyrrolidin-1-yl]-(5-methylimidazo[5,1-b][1,3,4]thiadiazol-2-yl)methanone | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH [(S)-2-(4-Chloro-phenyl)-pyrrolidin-1-yl]-(5-methyl-imidazo[5,1-b][1,3,4]thiadiazol-2-yl)-methanone | PDB:5ICP | ||||
| Method | X-ray diffraction | Resolution | 2.18 Å | Mutation | No | [11] |
| PDB Sequence |
MDYDFKVKLS
10 SERERVEDLF20 EYEGCKVGRG30 TYGHVYKAKR40 KDGKDDKDYA50 LKQIEGTGIS 60 MSACREIALL70 RELKHPNVIS80 LQKVFLSHAD90 RKVWLLFDYA100 EHDLWHIIKF 110 HRASKLPRGM127 VKSLLYQILD137 GIHYLHANWV147 LHRDLKPANI157 LVMGEGPERG 167 RVKIADMGFA177 RLFNSPLKVV195 TFWYRAPELL205 LGARHYTKAI215 DIWAIGCIFA 225 ELLTSEPIFH235 CRQESNPYHH249 DQLDRIFNVM259 GFPADKDWED269 IKKMPEHSTL 279 MKDFRRNTYT289 NCSLIKYMEK299 HKVKPDSKAF309 HLLQKLLTMD319 PIKRITSEQA 329 MQDPYFLEDP339 LPTSDVFAGC349 QIPYPKREFL359 TEE
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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 .69Z or .69Z2 or .69Z3 or :369Z;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:155 or .A:156 or .A:158 or .A:172 or .A:173 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 8-[3-(3-Azanyl-2~{h}-Indazol-6-Yl)-5-Chloranyl-Pyridin-4-Yl]-2,8-Diazaspiro[4.5]decan-1-One | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH 8-[3-(3-Amino-1H-indazol-6-yl)-5-chloro- pyridine-4-yl]-2,8-diaza-spiro[4.5]decan-1-one | PDB:5FGK | ||||
| Method | X-ray diffraction | Resolution | 2.36 Å | Mutation | No | [14] |
| PDB Sequence |
MDYDFKVKLS
10 SERERVEDLF20 EYEGCKVGRG30 TYGHVYKAKR40 KDGKDDKDYA50 LKQIEGTGIS 60 MSACREIALL70 RELKHPNVIS80 LQKVFLSHAD90 RKVWLLFDYA100 EHDLWHIIKF 110 HRAVQLPRGM127 VKSLLYQILD137 GIHYLHANWV147 LHRDLKPANI157 LVMGEGPERG 167 RVKIADMGFA177 VTFWYRAPEL204 LLGARHYTKA214 IDIWAIGCIF224 AELLTSEPIF 234 HCRQPYHHDQ251 LDRIFNVMGF261 PADKDWEDIK271 KMPEHSTLMK281 DFRRNTYTNC 291 SLIKYMEKHK301 VKPDSKAFHL311 LQKLLTMDPI321 KRITSEQAMQ331 DPYFLEDPLP 341 TSDVFAGCQI351 PYPKREFLTE361 E
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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 .5XG or .5XG2 or .5XG3 or :35XG;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:66 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:106 or .A:155 or .A:156 or .A:158 or .A:172 or .A:173 or .A:356; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 8-[3-Chloranyl-5-[1-Methyl-2,2-Bis(Oxidanylidene)-3~{h}-2,1-Benzothiazol-5-Yl]pyridin-4-Yl]-1-Oxa-3,8-Diazaspiro[4.5]decan-2-One | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH 8-[3-Chloro-5-(1-methyl-2,2-dioxo-2, 3-dihydro-1H-2l6-benzo[c]isothiazol-5-yl)-pyridin- 4-yl]-1-oxa-3,8-diaza-spiro[4.5]decan-2-one | PDB:5HBE | ||||
| Method | X-ray diffraction | Resolution | 2.38 Å | Mutation | No | [14] |
| PDB Sequence |
KMDYDFKVKL
9 SSERERVEDL19 FEYEGCKVGR29 GTYGHVYKAK39 RKDGKDDKDY49 ALKQIEGTGI 59 SMSACREIAL69 LRELKHPNVI79 SLQKVFLSHA89 DRKVWLLFDY99 AEHDLWHIIK 109 FHRASKANQL123 PRGMVKSLLY133 QILDGIHYLH143 ANWVLHRDLK153 PANILVMGEG 163 PERGRVKIAD173 MGFARLFNSP183 LKVTFWYRAP202 ELLLGARHYT212 KAIDIWAIGC 222 IFAELLTSEP232 IFHCRQSNPY247 HHDQLDRIFN257 VMGFPADKDW267 EDIKKMPEHS 277 TLMKDFRRNT287 YTNCSLIKYM297 EKHKVKPDSK307 AFHLLQKLLT317 MDPIKRITSE 327 QAMQDPYFLE337 DPLPTSDVFA347 GCQIPYPKRE357 FLTE
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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 .5Y6 or .5Y62 or .5Y63 or :35Y6;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:105 or .A:106 or .A:155 or .A:158 or .A:172 or .A:173 or .A:356; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 5-[5-Chloranyl-4-[1-(2-Methoxyethyl)-1,8-Diazaspiro[4.5]decan-8-Yl]pyridin-3-Yl]-1-Methyl-3~{h}-2,1-Benzothiazole 2,2-Dioxide | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH 5-{5-Chloro-4-[1-(2-methoxy-ethyl)-1,8-diaza-spiro[4.5]dec-8-yl]-pyridin-3-yl}-1-methyl-1,3-dihydro-benzo[c]isothiazole 2,2-dioxide | PDB:5HBH | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [14] |
| PDB Sequence |
DKMDYDFKVK
8 LSSERERVED18 LFEYEGCKVG28 RGTYGHVYKA38 KRKDGKDDKD48 YALKQIEGTG 58 ISMSACREIA68 LLRELKHPNV78 ISLQKVFLSH88 ADRKVWLLFD98 YAEHDLWHII 108 KFHRASQLPR125 GMVKSLLYQI135 LDGIHYLHAN145 WVLHRDLKPA155 NILVMGEGPE 165 RGRVKIADMG175 FARLVVTFWY199 RAPELLLGAR209 HYTKAIDIWA219 IGCIFAELLT 229 SEPIFHCRQE239 PYHHDQLDRI255 FNVMGFPADK265 DWEDIKKMPE275 HSTLMKDFRR 285 NTYTNCSLIK295 YMEKHKVKPD305 SKAFHLLQKL315 LTMDPIKRIT325 SEQAMQDPYF 335 LEDPLPTSDV345 FAGCQIPYPK355 REFLTE
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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 .5Y7 or .5Y72 or .5Y73 or :35Y7;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:66 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:105 or .A:106 or .A:155 or .A:156 or .A:158 or .A:172 or .A:173 or .A:176 or .A:356; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL27
3.515
GLY28
4.328
TYR32
3.276
VAL35
3.665
ALA50
3.355
LYS52
3.136
GLU66
4.665
ILE79
4.468
PHE97
3.615
ASP98
3.654
TYR99
4.023
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| Ligand Name: 8-(2-amino-3-chloro-5-(1-methyl-1H-indazol-5-yl)pyridin-4-yl)-2,8-diazaspiro[4.5]decan-1-one | Ligand Info | |||||
| Structure Description | CDK8-CYCC IN COMPLEX WITH 8-[2-Amino-3-chloro-5-(1-methyl-1H-indazol-5-yl)-pyridin-4-yl]-2,8-diaza-spiro[4.5]decan-1-one | PDB:5HBJ | ||||
| Method | X-ray diffraction | Resolution | 3.00 Å | Mutation | No | [14] |
| PDB Sequence |
DKMDYDFKVK
8 LSSERERVED18 LFEYEGCKVG28 RGTYGHVYKA38 KRKDGKDDKD48 YALKQIEGTG 58 ISMSACREIA68 LLRELKHPNV78 ISLQKVFLSH88 ADRKVWLLFD98 YAEHDLWHII 108 KFHRASKAVQ122 LPRGMVKSLL132 YQILDGIHYL142 HANWVLHRDL152 KPANILVMGE 162 GPERGRVKIA172 DMGFLFNSPL184 VTFWYRAPEL204 LLGARHYTKA214 IDIWAIGCIF 224 AELLTSEPIF234 HCRQSNPYHH249 DQLDRIFNVM259 GFPADKDWED269 IKKMPEHSTL 279 MKDFRRNTYT289 NCSLIKYMEK299 HKVKPDSKAF309 HLLQKLLTMD319 PIKRITSEQA 329 MQDPYFLEDP339 LPTSDVFAGC349 QIPYPKREFL359 TE
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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 .5Y8 or .5Y82 or .5Y83 or :35Y8;style chemicals stick;color identity;select .A:27 or .A:28 or .A:32 or .A:35 or .A:50 or .A:52 or .A:66 or .A:79 or .A:97 or .A:98 or .A:99 or .A:100 or .A:103 or .A:106 or .A:155 or .A:156 or .A:158 or .A:172 or .A:173 or .A:356; 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 | The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder. J Mol Biol. 2011 Sep 16;412(2):251-66. | ||||
| REF 2 | A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nat Chem Biol. 2015 Dec;11(12):973-980. | ||||
| REF 3 | A precisely positioned MED12 activation helix stimulates CDK8 kinase activity. Proc Natl Acad Sci U S A. 2020 Feb 11;117(6):2894-2905. | ||||
| REF 4 | Selective and Potent CDK8/19 Inhibitors Enhance NK-Cell Activity and Promote Tumor Surveillance. Mol Cancer Ther. 2020 Apr;19(4):1018-1030. | ||||
| REF 5 | Development of a Potent, Specific CDK8 Kinase Inhibitor Which Phenocopies CDK8/19 Knockout Cells. ACS Med Chem Lett. 2016 Jan 6;7(3):223-8. | ||||
| REF 6 | Design and Development of a Series of Potent and Selective Type II Inhibitors of CDK8. ACS Med Chem Lett. 2016 Apr 5;7(6):595-600. | ||||
| REF 7 | Mediator kinase inhibition further activates super-enhancer-associated genes in AML. Nature. 2015 Oct 8;526(7572):273-276. | ||||
| REF 8 | Structure-kinetic relationship study of CDK8/CycC specific compounds. Proc Natl Acad Sci U S A. 2013 May 14;110(20):8081-6. | ||||
| REF 9 | Pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives as CDK8 inhibitors. Eur J Med Chem. 2020 Sep 1;201:112443. | ||||
| REF 10 | Discovery of potent and selective CDK8 inhibitors through FBDD approach. Bioorg Med Chem Lett. 2017 Sep 15;27(18):4488-4492. | ||||
| REF 11 | Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J Med Chem. 2016 Oct 27;59(20):9337-9349. | ||||
| REF 12 | CDK8-CYCC IN COMPLEX WITH [6-Hydroxy-3-(3-methyl-benzyl)-1H-indazol-5-yl]-((S)-3-hydroxy-pyrrolidin-1-yl)-methanone | ||||
| REF 13 | 2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19. ACS Med Chem Lett. 2016 Mar 28;7(6):573-8. | ||||
| REF 14 | Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. J Med Chem. 2016 Feb 11;59(3):1078-101. | ||||
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