Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T89361 | Target Info | |||
| Target Name | Cyclin-dependent kinase 6 (CDK6) | ||||
| Synonyms | Serine/threonine-protein kinase PLSTIRE; Serine/threonine protein kinase PLSTIRE; Cell division protein kinase 6; CDKN6 | ||||
| Target Type | Successful Target | ||||
| Gene Name | CDK6 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Abemaciclib | Ligand Info | |||||
| Structure Description | The X-ray co-crystal structure of human CDK6 and Abemaciclib. | PDB:5L2S | ||||
| Method | X-ray diffraction | Resolution | 2.27 Å | Mutation | No | [1] |
| PDB Sequence |
QQYECVAEIG
20 EGAYGKVFKA30 RDLKNGGRFV40 ALKRVRVPLS57 TIREVAVLRH67 LETFEHPNVV 77 RLFDVCTKLT95 LVFEHVDQDL105 TTYLDKVPEP115 GVPTETIKDM125 MFQLLRGLDF 135 LHSHRVVHRD145 LKPQNILVTS155 SGQIKLADFG165 LAVTLWYRAP188 EVLLQSSYAT 198 PVDLWSVGCI208 FAEMFRRKPL218 FRGSSDVDQL228 GKILDVIGLP238 GEEDWPRDVA 248 LPRQAFHSKS258 AQPIEKFVTD268 IDELGKDLLL278 KCLTFNPAKR288 ISAYSALSHP 298 YFQ
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GLU18
4.164
ILE19
2.439
GLY20
3.300
GLU21
4.733
TYR24
2.675
VAL27
3.053
ALA41
3.586
LYS43
2.907
VAL77
3.252
PHE98
3.064
GLU99
2.310
|
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| Ligand Name: Palbociclib | Ligand Info | |||||
| Structure Description | The X-ray co-crystal structure of human CDK6 and Palbociclib. | PDB:5L2I | ||||
| Method | X-ray diffraction | Resolution | 2.75 Å | Mutation | No | [1] |
| PDB Sequence |
DQQYECVAEI
19 GEGAYGKVFK29 ARDLKNGGRF39 VALKRVRPLS57 TIREVAVLRH67 LETFEHPNVV 77 RLFDVCTKLT95 LVFEHVDQDL105 TTYLDKVPEP115 GVPTETIKDM125 MFQLLRGLDF 135 LHSHRVVHRD145 LKPQNILVTS155 SGQIKLADFG165 LVTLWYRAPE189 VLLQSSYATP 199 VDLWSVGCIF209 AEMFRRKPLF219 RGSSDVDQLG229 KILDVIGLPG239 EEDWPRDVAL 249 PRQAFKSAQP261 IEKFVTDIDE271 LGKDLLLKCL281 TFNPAKRISA291 YSALSHPYFQ 301
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GLU18
4.197
ILE19
2.670
GLY20
3.575
TYR24
2.805
VAL27
2.493
ALA41
3.090
LYS43
3.867
VAL77
3.258
PHE98
2.948
GLU99
2.392
HIS100
3.550
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: LEE011 | Ligand Info | |||||
| Structure Description | The X-ray co-crystal structure of human CDK6 and Ribociclib. | PDB:5L2T | ||||
| Method | X-ray diffraction | Resolution | 2.37 Å | Mutation | No | [1] |
| PDB Sequence |
QQYECVAEIG
20 EGAYGKVFKA30 RDLKNGGRFV40 ALKRVRVSTI59 REVAVLRHLE69 TFEHPNVVRL 79 FDVCTKLTLV97 FEHVDQDLTT107 YLDKVPEPGV117 PTETIKDMMF127 QLLRGLDFLH 137 SHRVVHRDLK147 PQNILVTSSG157 QIKLADFGLA167 VTLWYRAPEV190 LLQSSYATPV 200 DLWSVGCIFA210 EMFRRKPLFR220 GSSDVDQLGK230 ILDVIGLPGE240 EDWPRDVALP 250 RQAFHSKSAQ260 PIEKFVTDID270 ELGKDLLLKC280 LTFNPAKRIS290 AYSALSHPYF 300 Q
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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 .6ZZ or .6ZZ2 or .6ZZ3 or :36ZZ;style chemicals stick;color identity;select .A:19 or .A:20 or .A:27 or .A:41 or .A:42 or .A:43 or .A:77 or .A:96 or .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:106 or .A:107 or .A:149 or .A:150 or .A:152 or .A:162 or .A:163 or .A:164 or .A:166; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE19
2.938
GLY20
3.483
VAL27
3.056
ALA41
3.653
LEU42
4.909
LYS43
3.079
VAL77
3.085
LEU96
4.327
PHE98
2.984
GLU99
2.413
HIS100
3.413
VAL101
1.946
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| Ligand Name: 3,7,3',4'-TETRAHYDROXYFLAVONE | Ligand Info | |||||
| Structure Description | Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin | PDB:1XO2 | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [2] |
| PDB Sequence |
QQYECVAEIG
20 EGAYGKVFKA30 RDLKNGGRFV40 ALKRVRVQTG50 EEGMPLSTIR60 EVAVLRHLET 70 FEHPNVVRLF80 DVCTVSRETK93 LTLVFEHVDQ103 DLTTYLDKVP113 EPGVPTETIK 123 DMMFQLLRGL133 DFLHSHRVVH143 RDLKPQNILV153 TSSGQIKLAD163 FGLARIYSFQ 173 MALTSVVVTL183 WYRAPEVLLQ193 SSYATPVDLW203 SVGCIFAEMF213 RRKPLFRGSS 223 DVDQLGKILD233 VIGLPGEEDW243 PRDVALPRQA253 FHAQPIEKFV266 TDIDELGKDL 276 LLKCLTFNPA286 KRISAYSALS296 HPYFQDLER
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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 .FSE or .FSE2 or .FSE3 or :3FSE;style chemicals stick;color identity;select .B:19 or .B:20 or .B:27 or .B:41 or .B:43 or .B:61 or .B:77 or .B:98 or .B:99 or .B:100 or .B:101 or .B:103 or .B:104 or .B:149 or .B:150 or .B:152 or .B:162 or .B:163 or .B:164; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 9-Cyclopentyl-N-(5-Piperazin-1-Ylpyridin-2-Yl)pyrido[4,5]pyrrolo[1,2-D]pyrimidin-2-Amine | Ligand Info | |||||
| Structure Description | Crystal structure of a CDK6/Vcyclin complex with inhibitor bound | PDB:4TTH | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [3] |
| PDB Sequence |
CVAEIGEKVF
28 KARDLKNGRF39 VALKRVRVEG53 MPLSTIREVA63 VLRHLETFEH73 PNVVRLFDVC 83 TTKLTLVFEH100 VDQDLTTYLD110 KVPEPGVPTE120 TIKDMMFQLL130 RGLDFLHSHR 140 VVHRDLKPQN150 ILVTSSGQIK160 LADFGLARIY170 SFQMALTSVV180 VTLWYRAPEV 190 LLQSSYATPV200 DLWSVGCIFA210 EMFRRKPLFR220 GSSDVDQLGK230 ILDVIGLPGE 240 EDWPPIEKFD268 IDELGKDLLL278 KCLTFNPAKR288 ISAYSALSHP298 YFQDLE |
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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 .24V or .24V2 or .24V3 or :324V;style chemicals stick;color identity;select .B:18 or .B:19 or .B:20 or .B:27 or .B:41 or .B:61 or .B:77 or .B:98 or .B:99 or .B:100 or .B:101 or .B:102 or .B:103 or .B:104 or .B:107 or .B:149 or .B:150 or .B:152 or .B:162 or .B:163; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: (2S)-2-({6-[(3-Amino-5-chlorophenyl)amino]-9-isopropyl-9H-purin-2-YL}amino)-3-methylbutan-1-OL | Ligand Info | |||||
| Structure Description | X-ray structure of human CDK6-Vcyclinwith the inhibitor aminopurvalanol | PDB:2F2C | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [4] |
| PDB Sequence |
ADQQYECAEI
19 GGKVFKARDL33 KNGGRFVALK43 RVRVQTGEEG53 MPLSTIREVA63 VLRHLETFEH 73 PNVVRLFDVC83 TVSTDRETKL94 TLVFEHVDQD104 LTTYLDKVPE114 PGVPTETIKD 124 MMFQLLRGLD134 FLHSHRVVHR144 DLKPQNILVT154 SSGQIKLADF164 GLARIYSFQM 174 ALTSVVVTLW184 YRAPEVLLQS194 SYATPVDLWS204 VGCIFAEMFR214 RKPLFRGSSD 224 VDQLGKILDV234 IGLPGEEDWP244 QAFAQPIEKF265 VTDIDELGKD275 LLLKCLTFNP 285 AKRISAYSAL295 SHPYFQDLER305
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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 .AP9 or .AP92 or .AP93 or :3AP9;style chemicals stick;color identity;select .B:19 or .B:20 or .B:27 or .B:41 or .B:43 or .B:77 or .B:98 or .B:99 or .B:100 or .B:101 or .B:102 or .B:103 or .B:104 or .B:107 or .B:149 or .B:150 or .B:152 or .B:162; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 1h-Benzimidazol-2-Yl(1h-Pyrrol-2-Yl)methanone | Ligand Info | |||||
| Structure Description | Liganded X-ray crystal structure of cyclin dependent kinase 6 (CDK6) | PDB:4AUA | ||||
| Method | X-ray diffraction | Resolution | 2.31 Å | Mutation | No | [5] |
| PDB Sequence |
QQYECVAEIG
20 EGAGKVFKAR31 DLKNGGRFVA41 LKRSTIREVA63 VLRHLETFEH73 PNVVRLFDVC 83 TKLTLVFEHV101 DQDLTTYLDK111 VPEPGVPTET121 IKDMMFQLLR131 GLDFLHSHRV 141 VHRDLKPQNI151 LVTSSGQIKL161 ADFGLATLWY185 RAPEVLLQSS195 YATPVDLWSV 205 GCIFAEMFRR215 KPLFRGSSDV225 DQLGKILDVI235 GLPGEEDWPR245 DVALPRQAFH 255 SKSAQPIEKF265 VTDIDELGKD275 LLLKCLTFNP285 AKRISAYSAL295 SHPYFQ |
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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 .4AU or .4AU2 or .4AU3 or :34AU;style chemicals stick;color identity;select .A:19 or .A:20 or .A:27 or .A:41 or .A:43 or .A:77 or .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:107 or .A:149 or .A:152 or .A:162 or .A:163; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4-[3-(1-Methylethyl)-1h-Pyrazol-4-Yl]-N-(1-Methylpiperidin-4-Yl)pyrimidin-2-Amine | Ligand Info | |||||
| Structure Description | CDK6 (monomeric) in complex with inhibitor | PDB:3NUP | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [6] |
| PDB Sequence |
QYECVAEIGG
25 KVFKARDLKN35 GGRFVALKRV45 LSTIREVAVL65 RHLETFEHPN75 VVRLFDVCTV 85 KLTLVFEHVD102 QDLTTYLDKV112 PEPGVPTETI122 KDMMFQLLRG132 LDFLHSHRVV 142 HRDLKPQNIL152 VTSSGQIKLA162 DFGLVTLWYR186 APEVLLQSSY196 ATPVDLWSVG 206 CIFAEMFRRK216 PLFRGSSDVD226 QLGKILDVIG236 LPGEEDWPRD246 VALPRQAFHS 258 AQPIEKFVTD268 IDELGKDLLL278 KCLTFNPAKR288 ISAYSALSHP298 YF |
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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 .3NU or .3NU2 or .3NU3 or :33NU;style chemicals stick;color identity;select .A:19 or .A:20 or .A:27 or .A:41 or .A:43 or .A:77 or .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:149 or .A:150 or .A:152 or .A:162 or .A:163; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 4-[5-Chloro-3-(1-Methylethyl)-1h-Pyrazol-4-Yl]-N-(5-Piperazin-1-Ylpyridin-2-Yl)pyrimidin-2-Amine | Ligand Info | |||||
| Structure Description | CDK6 (monomeric) in complex with inhibitor | PDB:3NUX | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [6] |
| PDB Sequence |
DQQYECVAEI
19 GEGAGKVFKA30 RDLKNGGRFV40 ALKRVRPLST58 IREVAVLRHL68 ETFEHPNVVR 78 LFDVCTKLTL96 VFEHVDQDLT106 TYLDKVPEPG116 VPTETIKDMM126 FQLLRGLDFL 136 HSHRVVHRDL146 KPQNILVTSS156 GQIKLADFGL166 AVTLWYRAPE189 VLLQSSYATP 199 VDLWSVGCIF209 AEMFRRKPLF219 RGSSDVDQLG229 KILDVIGLPG239 EEDWPRDVAL 249 PRQAFHKSAQ260 PIEKFVTDID270 ELGKDLLLKC280 LTFNPAKRIS290 AYSALSHPYF 300 Q
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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 .3NV or .3NV2 or .3NV3 or :33NV;style chemicals stick;color identity;select .A:19 or .A:20 or .A:27 or .A:41 or .A:43 or .A:77 or .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:104 or .A:107 or .A:149 or .A:150 or .A:152 or .A:162 or .A:163; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: {5-[4-(Dimethylamino)piperidin-1-Yl]-1h-Imidazo[4,5-B]pyridin-2-Yl}[2-(Isoquinolin-4-Yl)pyridin-4-Yl]methanone | Ligand Info | |||||
| Structure Description | CDK6 (monomeric) in complex with inhibitor | PDB:4EZ5 | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [5] |
| PDB Sequence |
QQYECVAEIG
20 EGAGKVFKAR31 DLKNGGRFVA41 LKRVPLSTIR60 EVAVLRHLET70 FEHPNVVRLF 80 DVCTKLTLVF98 EHVDQDLTTY108 LDKVPEPGVP118 TETIKDMMFQ128 LLRGLDFLHS 138 HRVVHRDLKP148 QNILVTSSGQ158 IKLADFGLAV181 TLWYRAPEVL191 LQSSYATPVD 201 LWSVGCIFAE211 MFRRKPLFRG221 SSDVDQLGKI231 LDVIGLPGEE241 DWPRDVALPR 251 QAFHSAQPIE263 KFVTDIDELG273 KDLLLKCLTF283 NPAKRISAYS293 ALSHPYFQ |
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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 .0RS or .0RS2 or .0RS3 or :30RS;style chemicals stick;color identity;select .A:18 or .A:19 or .A:27 or .A:41 or .A:43 or .A:77 or .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:107 or .A:149 or .A:150 or .A:152 or .A:162 or .A:163; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: Cdk4/6-IN-3 | Ligand Info | |||||
| Structure Description | CDK6 in complex with Cpd24 N-(5-(6-ethyl-2,6-diazaspiro[3.3]heptan-2-yl)pyridin-2-yl)-5-fluoro-4-(4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl)pyrimidin-2-amine | PDB:6OQO | ||||
| Method | X-ray diffraction | Resolution | 1.98 Å | Mutation | No | [7] |
| PDB Sequence |
QQYECVAEIG
20 EGAYGKVFKA30 RDLKNGGRFV40 ALKRVRVQTG50 GMPLSTIREV62 AVLRHLETFE 72 HPNVVRLFDV82 CTVKLTLVFE99 HVDQDLTTYL109 DKVPEPGVPT119 ETIKDMMFQL 129 LRGLDFLHSH139 RVVHRDLKPQ149 NILVTSSGQI159 KLADFGLAVT182 LWYRAPEVLL 192 QSSYATPVDL202 WSVGCIFAEM212 FRRKPLFRGS222 SDVDQLGKIL232 DVIGLPGEED 242 WPRDVALPRQ252 AFHSKSAQPI262 EKFVTDIDEL272 GKDLLLKCLT282 FNPAKRISAY 292 SALSHPYFQ
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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 .N1J or .N1J2 or .N1J3 or :3N1J;style chemicals stick;color identity;select .A:19 or .A:20 or .A:24 or .A:27 or .A:41 or .A:43 or .A:77 or .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:107 or .A:149 or .A:150 or .A:152 or .A:162 or .A:163; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 5-fluoro-N-[5-(4-methylpiperazin-1-yl)pyridin-2-yl]-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]pyrimidin-2-amine | Ligand Info | |||||
| Structure Description | CDK6 in complex with Cpd13 (R)-5-fluoro-4-(4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl)-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)pyrimidin-2-amine | PDB:6OQL | ||||
| Method | X-ray diffraction | Resolution | 2.71 Å | Mutation | No | [7] |
| PDB Sequence |
QQYECVAEIG
20 EGAYGKVFKA30 RDLKNGGRFV40 ALKRVRVPLS57 TIREVAVLRH67 LETFEHPNVV 77 RLFDVCTKLT95 LVFEHVDQDL105 TTYLDKVPEP115 GVPTETIKDM125 MFQLLRGLDF 135 LHSHRVVHRD145 LKPQNILVTS155 SGQIKLADFG165 LAVTLWYRAP188 EVLLQSSYAT 198 PVDLWSVGCI208 FAEMFRRKPL218 FRGSSDVDQL228 GKILDVIGLP238 GEEDWPRDVA 248 LPRQAFHSKS258 AQPIEKFVTD268 IDELGKDLLL278 KCLTFNPAKR288 ISAYSALSHP 298 YFQ
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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 .N1A or .N1A2 or .N1A3 or :3N1A;style chemicals stick;color identity;select .A:19 or .A:20 or .A:24 or .A:27 or .A:41 or .A:43 or .A:77 or .A:98 or .A:99 or .A:100 or .A:101 or .A:102 or .A:103 or .A:104 or .A:107 or .A:149 or .A:150 or .A:152 or .A:162 or .A:163; 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 | Spectrum and Degree of CDK Drug Interactions Predicts Clinical Performance. Mol Cancer Ther. 2016 Oct;15(10):2273-2281. | ||||
| REF 2 | Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin. J Med Chem. 2005 Feb 10;48(3):737-43. | ||||
| REF 3 | Discovery of AMG 925, a FLT3 and CDK4 dual kinase inhibitor with preferential affinity for the activated state of FLT3. J Med Chem. 2014 Apr 24;57(8):3430-49. | ||||
| REF 4 | Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition. J Med Chem. 2006 Jun 29;49(13):3826-31. | ||||
| REF 5 | Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and Orally Active CDK4/6 Inhibitors. ACS Med Chem Lett. 2012 May 17;3(6):445-9. | ||||
| REF 6 | 4-(Pyrazol-4-yl)-pyrimidines as selective inhibitors of cyclin-dependent kinase 4/6. J Med Chem. 2010 Nov 25;53(22):7938-57. | ||||
| REF 7 | Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma. Bioorg Med Chem Lett. 2019 Aug 15;29(16):2294-2301. | ||||
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