Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T31406 | Target Info | |||
| Target Name | Hematopoietic cell kinase (HCK) | ||||
| Synonyms | p61Hck; p59Hck; p59-HCK/p60-HCK; Tyrosine-protein kinase HCK; Hemopoietic cell kinase | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | HCK | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | GS-9005 | Ligand Info | |||
| Canonical SMILES | CN1CCN(CC1)C2CCC(CC2)N3C=C(C4=C(N=CN=C43)N)C5=CC=C(C=C5)OC6=CC=CC=C6 | ||||
| InChI | 1S/C29H34N6O/c1-33-15-17-34(18-16-33)22-9-11-23(12-10-22)35-19-26(27-28(30)31-20-32-29(27)35)21-7-13-25(14-8-21)36-24-5-3-2-4-6-24/h2-8,13-14,19-20,22-23H,9-12,15-18H2,1H3,(H2,30,31,32) | ||||
| InChIKey | FDVSOQRNTAPCHB-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 6539952 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3VS3 Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor 7-[trans-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine | ||||||
| Method | X-ray diffraction | Resolution | 2.17 Å | Mutation | Yes | [1] |
| PDB Sequence |
RIIVVALYDY
94 EAIHHEDLSF104 QKGDQMVVLE114 ESGEWWKARS124 LATRKEGYIP134 SNYVARVDSL 144 ETEEWFFKGI154 SRKDAERQLL164 APGNMLGSFM174 IRDSETTKGS184 YSLSVRDYDP 194 RQGDTVKHYK204 IRTLDNGGFY214 ISPRSTFSTL224 QELVDHYKKG234 NDGLCQKLSV 244 PCMSSKPQKP254 WEKDAWEIPR264 ESLKLEKKLG274 AGQFGEVWMA284 TYNKHTKVAV 294 KTMKPGSMSV304 EAFLAEANVM314 KTLQHDKLVK324 LHAVVTKEPI334 YIITEFMAKG 344 SLLDFLKSDE354 GSKQPLPKLI364 DFSAQIAEGM374 AFIEQRNYIH384 RDLRAANILV 394 SASLVCKIAD404 FGLARVIFPI426 KWTAPEAINF436 GSFTIKSDVW446 SFGILLMEIV 456 TYGRIPYPGM466 SNPEVIRALE476 RGYRMPRPEN486 CPEELYNIMM496 RCWKNRPEER 506 PTFEYIQSVL516 DDFYTATESQ526 EEIP
|
|||||
|
|
LEU273
3.606
GLY274
4.065
VAL281
3.625
ALA293
3.181
LYS295
3.500
MET314
3.403
VAL323
3.452
LEU325
3.580
ILE336
3.863
THR338
3.189
GLU339
3.179
|
|||||
| PDB ID: 4LUE Crystal Structure of HCK in complex with 7-[trans-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (resulting from displacement of SKF86002) | ||||||
| Method | X-ray diffraction | Resolution | 3.04 Å | Mutation | Yes | [2] |
| PDB Sequence |
RIIVVALYDY
94 EAIHHEDLSF104 QKGDQMVVLE114 ESGEWWKARS124 LATRKEGYIP134 SNYVARVDSL 144 ETEEWFFKGI154 SRKDAERQLL164 APGNMLGSFM174 IRDSETTKGS184 YSLSVRDYDP 194 RQGDTVKHYK204 IRTGFYISPR218 STFSTLQELV228 DHYKKGNDGL238 CQKLSVPCMS 248 SKPQKPWEKD258 AWEIPRESLK268 LEKKLGAGQF278 GEVWMATYNK288 HTKVAVKTMK 298 PGSLAEANVM314 KTLQHDKLVK324 LHAVVTKEPI334 YIITEFMAKG344 SLLDFLKSDE 354 GSKQPLPKLI364 DFSAQIAEGM374 AFIEQRNYIH384 RDLRAANILV394 SASLVCKIAD 404 FGLARVIPIK427 WTAPEAINFG437 SFTIKSDVWS447 FGILLMEIVT457 YGRIPYPGMS 467 NPEVIRALER477 GYRMPRPENC487 PEELYNIMMR497 CWKNRPEERP507 TFEYIQSVLD 517 DFYTATESQE528 EI
|
|||||
|
|
LEU273
3.844
GLY274
4.640
VAL281
3.511
ALA293
3.417
VAL294
4.975
LYS295
3.589
MET314
3.912
VAL323
3.552
LEU325
4.359
ILE336
3.728
THR338
3.036
|
|||||
| PDB ID: 5ZJ6 Crystal structure of HCK kinase complexed with a pyrrolo-pyrimidine inhibitor 7-[trans-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine | ||||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [3] |
| PDB Sequence |
KPWEKDAWEI
262 PRESLKLEKK272 LGAGQFGEVW282 MATYNKHTKV292 AVKTMKPGSM302 SVEAFLAEAN 312 VMKTLQHDKL322 VKLHAVVTKE332 PIYIITEFMA342 KGSLLDFLKS352 DEGSKQPLPK 362 LIDFSAQIAE372 GMAFIEQRNY382 IHRDLRAANI392 LVSASLVCKI402 ADFGLARVIE 412 DNEYTAREGA422 KFPIKWTAPE432 AINFGSFTIK442 SDVWSFGILL452 MEIVTYGRIP 462 YPGMSNPEVI472 RALERGYRMP482 RPENCPEELY492 NIMMRCWKNR502 PEERPTFEYI 512 QSVLDDFYTA522 T
|
|||||
|
|
LEU273
3.501
GLY274
4.095
VAL281
3.663
ALA293
3.272
LYS295
3.447
MET314
4.157
VAL323
4.366
ILE336
3.872
THR338
3.055
GLU339
2.937
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | A pyrrolo-pyrimidine derivative targets human primary AML stem cells in vivo. Sci Transl Med. 2013 Apr 17;5(181):181ra52. | ||||
| REF 2 | Kinase crystal identification and ATP-competitive inhibitor screening using the fluorescent ligand SKF86002. Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):392-404. | ||||
| REF 3 | Phosphorylated and non-phosphorylated HCK kinase domains produced by cell-free protein expression. Protein Expr Purif. 2018 Oct;150:92-99. | ||||
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