Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T14597 | Target Info | |||
| Target Name | Erbb2 tyrosine kinase receptor (HER2) | ||||
| Synonyms | p185erbB2; Tyrosine kinase-type cell surface receptor HER2; Receptor tyrosine-protein kinase erbB-2; Proto-oncogene c-ErbB-2; Proto-oncogene Neu; NGL; NEU; Metastatic lymph node gene 19 protein; MLN19; MLN 19; HER2; CD340 | ||||
| Target Type | Successful Target | ||||
| Gene Name | ERBB2 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: TAK-285 | Ligand Info | |||||
| Structure Description | HER2 Kinase Domain Complexed with TAK-285 | PDB:3RCD | ||||
| Method | X-ray diffraction | Resolution | 3.21 Å | Mutation | No | [1] |
| PDB Sequence |
ALLRILKETE
719 LRKVKVLGSG729 AFGTVYKGIW739 IPDGENVKIP749 VAIKVLRPKA763 NKEILDEAYV 773 MAGVGSPYVS783 RLLGICLTST793 VQLVTQLMPY803 GCLLDHVREN813 RGRLGSQDLL 823 NWCMQIAKGM833 SYLEDVRLVH843 RDLAARNVLV853 KSPNHVKITD863 FGLVPIKWMA 890 LESILRRRFT900 HQSDVWSYGV910 TVWELMTFGA920 KPYDGIPARE930 IPDLLEKGER 940 LPQPPICTID950 VYMIMVKCWM960 IDSECRPRFR970 ELVSEFSRMA980 RDPQRFVVIQ 990 NLDSTFYRSL1008 LEDDDLVDAE1021 E
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LEU726
3.861
GLY727
3.461
SER728
4.358
GLY729
4.041
VAL734
3.439
ALA751
3.418
ILE752
4.305
LYS753
3.419
MET774
4.518
SER783
2.899
ARG784
3.675
LEU785
3.064
LEU796
3.465
|
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| Ligand Name: Beta-D-Mannose | Ligand Info | |||||
| Structure Description | HuA21-scFv in complex with the extracellular domain(ECD) of HER2 | PDB:6J71 | ||||
| Method | X-ray diffraction | Resolution | 2.92 Å | Mutation | No | [2] |
| PDB Sequence |
STQVCTGTDM
31 KLRLPASPET41 HLDMLRHLYQ51 GCQVVQGNLE61 LTYLPTNASL71 SFLQDIQEVQ 81 GYVLIAHNQV91 RQVPLQRLRI101 VRGTQLFEDN111 YALAVLDNGD121 PLNNTTPVTG 131 ASPGGLRELQ141 LRSLTEILKG151 GVLIQRNPQL161 CYQDTILWKD171 IFHKNNQLAL 181 TLIDTNRSRA191 CHPCSPMCKG201 SRCWGESSED211 CQSLTRTVCA221 GGCARCKGPL 231 PTDCCHEQCA241 AGCTGPKHSD251 CLACLHFNHS261 GICELHCPAL271 VTYNTDTFES 281 MPNPEGRYTF291 GASCVTACPY301 NYLSTDVGSC311 TLVCPLHNQE321 VTAEDGTQRC 331 EKCSKPCARV341 CYGLGMEHLR351 EVRAVTSANI361 QEFAGCKKIF371 GSLAFLPESF 381 DGDPASNTAP391 LQPEQLQVFE401 TLEEITGYLY411 ISAWPDSLPD421 LSVFQNLQVI 431 RGRILHNGAY441 SLTLQGLGIS451 WLGLRSLREL461 GSGLALIHHN471 THLCFVHTVP 481 WDQLFRNPHQ491 ALLHTANRPE501 DECVGEGLAC511 HQLCARGHCW521 GPGPTQCVNC 531 SQFLRGQECV541 EECRVLQGLP551 REYVNARHCL561 PCHPECQPQN571 GSVTCFGPEA 581 DQCVACAHYK591 DPPFCVARCP601 SGVKPDLSYM611 PIWKFPDEEG621 ACQPCPINCT 631 HSCVDLDD
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| Ligand Name: 2-{2-[4-({5-Chloro-6-[3-(Trifluoromethyl)phenoxy]pyridin-3-Yl}amino)-5h-Pyrrolo[3,2-D]pyrimidin-5-Yl]ethoxy}ethanol | Ligand Info | |||||
| Structure Description | Crystal Structure of the Kinase domain of Human HER2 (erbB2). | PDB:3PP0 | ||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | Yes | [3] |
| PDB Sequence |
APNQALLRIL
715 KETELRKVKV725 LGSGAFGTVY735 KGIWIPDGEN745 VKIPVAIKVL755 RENTSPKANK 765 EILDEAYVMA775 GVGSPYVSRL785 LGICLTSTVQ795 LVTQLMPYGC805 LLDHVRENRG 815 RLGSQDLLNW825 CMQIAKGMSY835 LEDVRLVHRD845 LAARNVLVKS855 PNHVKITDFG 865 LARLLDIDET875 EYHAGKVPIK887 WMALESILRR897 RFTHQSDVWS907 YGVTVWELMT 917 FGAKPYDGIP927 AREIPDLLEK937 GERLPQPPIC947 TIDVYMIMVK957 CWMIDSECRP 967 RFRELVSEFS977 RMARDPQRFV987 VIQNED
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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 .03Q or .03Q2 or .03Q3 or :303Q;style chemicals stick;color identity;select .A:726 or .A:728 or .A:729 or .A:730 or .A:734 or .A:751 or .A:752 or .A:753 or .A:767 or .A:770 or .A:771 or .A:774 or .A:783 or .A:784 or .A:785 or .A:796 or .A:797 or .A:798 or .A:799 or .A:800 or .A:801 or .A:804 or .A:805 or .A:849 or .A:850 or .A:852 or .A:862 or .A:863 or .A:864; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU726
3.432
SER728
4.268
GLY729
3.391
ALA730
4.875
VAL734
3.383
ALA751
3.130
ILE752
4.323
LYS753
3.446
ILE767
4.721
GLU770
3.374
ALA771
3.714
MET774
3.408
SER783
3.336
ARG784
4.485
LEU785
3.356
|
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| Ligand Name: 1-[4-[4-[3,5-Dichloro-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)anilino]pyrimido[5,4-d]pyrimidin-6-yl]piperazin-1-yl]-4-(3-fluoroazetidin-1-yl)butan-1-one | Ligand Info | |||||
| Structure Description | HER2 IN COMPLEX WITH A COVALENT INHIBITOR | PDB:7PCD | ||||
| Method | X-ray diffraction | Resolution | 1.77 Å | Mutation | No | [4] |
| PDB Sequence |
ALLRILKETE
719 LRKVKVLGSG729 AFGTVYKGIW739 IPDGENVKIP749 VAIKVLRENT759 SPKANKEILD 769 EAYVMAGVGS779 PYVSRLLGIC789 LTSTVQLVTQ799 LMPYGCLLDH809 VRENRGRLGS 819 QDLLNWCMQI829 AKGMSYLEDV839 RLVHRDLAAR849 NVLVKSPNHV859 KITDFGLARL 869 LDIDVPIKWM889 ALESILRRRF899 THQSDVWSYG909 VTVWELMTFG919 AKPYDGIPAR 929 EIPDLLEKGE939 RLPQPPICTI949 DVYMIMVKCW959 MIDSECRPRF969 RELVSEFSRM 979 ARDPQRFVVI989 QN
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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 .70I or .70I2 or .70I3 or :370I;style chemicals stick;color identity;select .A:726 or .A:727 or .A:734 or .A:751 or .A:752 or .A:753 or .A:767 or .A:771 or .A:774 or .A:783 or .A:784 or .A:785 or .A:796 or .A:797 or .A:798 or .A:799 or .A:800 or .A:801 or .A:804 or .A:805 or .A:807 or .A:808 or .A:849 or .A:852 or .A:862 or .A:863 or .A:864; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU726
3.609
GLY727
4.405
VAL734
3.614
ALA751
3.381
ILE752
4.629
LYS753
3.527
ILE767
4.538
ALA771
3.586
MET774
3.879
SER783
3.155
ARG784
3.945
LEU785
3.677
LEU796
3.200
VAL797
4.344
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| Ligand Name: (E)-N-[3-cyano-7-ethoxy-4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)anilino]quinolin-6-yl]-4-(dimethylamino)but-2-enamide | Ligand Info | |||||
| Structure Description | HER2 in complex with JBJ-08-178-01 | PDB:7JXH | ||||
| Method | X-ray diffraction | Resolution | 3.27 Å | Mutation | No | [5] |
| PDB Sequence |
PNQAQMRILK
716 ETELRKVKVL726 GSGAFGTVYK736 GIWIPDGENV746 KIPVAIKVLR756 ENTSPKANKE 766 ILDEAYVMAG776 VGSPYVSRLL786 GICLTSTVQL796 VTQLMPYGCL806 LDHVRENRGR 816 LGSQDLLNWC826 MQIAKGMSYL836 EDVRLVHRDL846 AARNVLVKSP856 NHVKITDFGL 866 AGKVPIKWMA890 LESILRRRFT900 HQSDVWSYGV910 TVWELMTFGA920 KPYDGIPARE 930 IPDLLEKGER940 LPQPPICTID950 VYMIMVKCWM960 IDSECRPRFR970 ELVSEFSRMA 980 RDPQRFVVIQ990 NEDLGP
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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 .VOY or .VOY2 or .VOY3 or :3VOY;style chemicals stick;color identity;select .B:726 or .B:734 or .B:751 or .B:752 or .B:753 or .B:770 or .B:774 or .B:783 or .B:784 or .B:785 or .B:796 or .B:798 or .B:799 or .B:800 or .B:801 or .B:802 or .B:803 or .B:804 or .B:805 or .B:807 or .B:808 or .B:811 or .B:849 or .B:852 or .B:862 or .B:863 or .B:864; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU726
3.485
VAL734
3.871
ALA751
3.685
ILE752
4.297
LYS753
3.184
GLU770
4.632
MET774
3.355
SER783
3.064
ARG784
4.154
LEU785
3.735
LEU796
3.602
THR798
3.170
GLN799
3.386
LEU800
3.300
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Design and synthesis of novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors bearing a pyrrolo[3,2-d]pyrimidine scaffold. J Med Chem. 2011 Dec 8;54(23):8030-50. | ||||
| REF 2 | Structural insight into a matured humanized monoclonal antibody HuA21 against HER2-overexpressing cancer cells. Acta Crystallogr D Struct Biol. 2019 Jun 1;75(Pt 6):554-563. | ||||
| REF 3 | Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein. J Biol Chem. 2011 May 27;286(21):18756-65. | ||||
| REF 4 | Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling. Nat Cancer. 2022 Jul;3(7):821-836. | ||||
| REF 5 | A Novel HER2-Selective Kinase Inhibitor Is Effective in HER2 Mutant and Amplified Non-Small Cell Lung Cancer. Cancer Res. 2022 Apr 15;82(8):1633-1645. | ||||
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