Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T59328 Target Info
Target Name Epidermal growth factor receptor (EGFR)
Synonyms Receptor tyrosine-protein kinase erbB-1; Proto-oncogene c-ErbB-1; HER1; ERBB1; ERBB
Target Type Successful Target
Gene Name EGFR
Biochemical Class Kinase
UniProt ID
EGFR_HUMAN
Ligand General Information  Top
Ligand Name (2R)-2-(5-fluoro-2-hydroxyphenyl)-2-{6-[4-(1-methylpiperidin-4-yl)phenyl]-1-oxo-1,3-dihydro-2H-isoindol-2-yl}-N-(1,3-thiazol-2-yl)acetamide Ligand Info
Canonical SMILES CN1CCC(CC1)C2=CC=C(C=C2)C3=CC4=C(CN(C4=O)C(C5=C(C=CC(=C5)F)O)C(=O)NC6=NC=CS6)C=C3
InChI 1S/C31H29FN4O3S/c1-35-13-10-21(11-14-35)19-2-4-20(5-3-19)22-6-7-23-18-36(30(39)25(23)16-22)28(26-17-24(32)8-9-27(26)37)29(38)34-31-33-12-15-40-31/h2-9,12,15-17,21,28,37H,10-11,13-14,18H2,1H3,(H,33,34,38)/t28-/m1/s1
InChIKey SYTVDTWRIZNVEW-MUUNZHRXSA-N
PubChem Compound ID 156595832
Drug Binding Sites of Target  Top
PDB ID: 7JXQ      EGFR kinase (T790M/V948R) in complex with allosteric inhibitor JBJ-09-063
Method X-ray diffraction Resolution 1.83 Å Mutation Yes [1]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPKANKEI
759
LDEAYVMASV
769
DNPHVCRLLG
779
ICLTSTVQLI
789
MQLMPFGCLL
799

DYVREHKDNI
809
GSQYLLNWCV
819
QIAKGMNYLE
829
DRRLVHRDLA
839
ARNVLVKTPQ
849

HVKITDFGLA
859
KLLGAEVPIK
879
WMALESILHR
889
IYTHQSDVWS
899
YGVTVWELMT
909

FGSKPYDGIP
919
ASEISSILEK
929
GERLPQPPIC
939
TIDVYMIMRK
949
CWMIDADSRP
959

KFRELIIEFS
969
KMARDPQRYL
979
VIQGDERMHL
989
PSPTDSNFYR
999
ALMDEEDM
Residue
Distance (Å)
VAL726
3.840
ALA743
3.471
ILE744
3.641
LYS745
3.313
LEU747
3.538
GLU749
4.304
THR751
4.232
ALA755
4.290
GLU758
4.347
ILE759
3.709
GLU762
3.809
ALA763
4.106
MET766
3.312
CYS775
3.514
Residue
Distance (Å)
ARG776
3.111
LEU777
3.026
LEU788
3.155
ILE789
4.338
MET790
3.452
THR854
4.168
ASP855
2.759
PHE856
2.754
GLY857
4.900
LEU858
3.350
LYS860
3.666
LEU861
3.572
ALA864
4.133
PDB ID: 7JXW      EGFR kinase (T790M/V948R) in complex with osimertinib and JBJ-09-063
Method X-ray diffraction Resolution 2.50 Å Mutation Yes [2]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELSP
753

KANKEILDEA
763
YVMASVDNPH
773
VCRLLGICLT
783
STVQLIMQLM
793
PFGCLLDYVR
803

EHKDNIGSQY
813
LLNWCVQIAK
823
GMNYLEDRRL
833
VHRDLAARNV
843
LVKTPQHVKI
853

TDFGLVPIKW
880
MALESILHRI
890
YTHQSDVWSY
900
GVTVWELMTF
910
GSKPYDGIPA
920

SEISSILEKG
930
ERLPQPPICT
940
IDVYMIMRKC
950
WMIDADSRPK
960
FRELIIEFSK
970

MARDPQRYLV
980
IQGDERMHLP
990
SPTDSNFYRA
1000
LMDEEDM
Residue
Distance (Å)
PHE723
4.121
VAL726
3.617
ALA743
2.863
ILE744
3.091
LYS745
2.499
LEU747
3.133
ALA755
4.437
GLU758
3.749
ILE759
3.314
GLU762
4.742
ALA763
4.533
Residue
Distance (Å)
MET766
3.002
CYS775
3.868
ARG776
3.131
LEU777
3.285
LEU788
3.322
ILE789
4.014
MET790
3.315
THR854
4.126
ASP855
3.008
PHE856
3.203
LEU858
3.500
PDB ID: 7K1H      EGFR L858R/V948R in complex with osimertinib and allosteric inhibitor JBJ-09-063
Method X-ray diffraction Resolution 2.60 Å Mutation Yes [2]
PDB Sequence
QALLRILKET
710
EFKKIKVLGS
720
GAFGTVYKGL
730
WIPEGEKVKI
740
PVAIKELREA
750

TSPKANKEIL
760
DEAYVMASVD
770
NPHVCRLLGI
780
CLTSTVQLIT
790
QLMPFGCLLD
800

YVREHKDNIG
810
SQYLLNWCVQ
820
IAKGMNYLED
830
RRLVHRDLAA
840
RNVLVKTPQH
850

VKITDFGRVP
877
IKWMALESIL
887
HRIYTHQSDV
897
WSYGVTVWEL
907
MTFGSKPYDG
917

IPASEISSIL
927
EKGERLPQPP
937
ICTIDVYMIM
947
RKCWMIDADS
957
RPKFRELIIE
967

FSKMARDPQR
977
YLVIQGDERM
987
HLPSPTDSNF
997
YRALMDEEDM
1007
D
Residue
Distance (Å)
PHE723
4.116
VAL726
3.714
ALA743
2.977
ILE744
3.578
LYS745
2.629
LEU747
3.724
GLU749
3.359
THR751
4.649
ALA755
3.960
GLU758
4.113
ILE759
3.494
GLU762
4.336
ALA763
4.105
Residue
Distance (Å)
MET766
3.536
CYS775
3.254
ARG776
2.809
LEU777
2.760
LEU788
3.424
ILE789
4.171
THR790
3.235
THR854
4.263
ASP855
3.075
PHE856
2.529
GLY857
4.539
ARG858
3.194
PDB ID: 7LG8      EGFR (T79M/V948R) in complex with naquotinib and an allosteric inhibitor
Method X-ray diffraction Resolution 2.93 Å Mutation Yes [3]
PDB Sequence
ALLRILKETE
711
FKKIKVLGSG
721
AFGTVYKGLW
731
IPEGEKVKIP
741
VAIKELREAT
751

SPKANKEILD
761
EAYVMASVDN
771
PHVCRLLGIC
781
LTSTVQLIMQ
791
LMPFGCLLDY
801

VREHKDNIGS
811
QYLLNWCVQI
821
AKGMNYLEDR
831
RLVHRDLAAR
841
NVLVKTPQHV
851

KITDFGLAKV
876
PIKWMALESI
886
LHRIYTHQSD
896
VWSYGVTVWE
906
LMTFGSKPYD
916

GIPASEISSI
926
LEKGERLPQP
936
PICTIDVYMI
946
MRKCWMIDAD
956
SRPKFRELII
966

EFSKMARDPQ
976
RYLVIQGDEN
996
FYRALMDEED
1006
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .VNS or .VNS2 or .VNS3 or :3VNS;style chemicals stick;color identity;select .A:726 or .A:743 or .A:744 or .A:745 or .A:747 or .A:749 or .A:755 or .A:758 or .A:759 or .A:762 or .A:763 or .A:766 or .A:775 or .A:776 or .A:777 or .A:788 or .A:789 or .A:790 or .A:854 or .A:855 or .A:856 or .A:858 or .A:860; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
VAL726
3.868
ALA743
3.138
ILE744
3.831
LYS745
3.420
LEU747
4.004
GLU749
3.722
ALA755
4.529
GLU758
3.639
ILE759
3.794
GLU762
3.661
ALA763
4.162
MET766
3.349
Residue
Distance (Å)
CYS775
3.521
ARG776
3.371
LEU777
3.219
LEU788
3.164
ILE789
4.526
MET790
3.567
THR854
4.276
ASP855
2.961
PHE856
3.137
LEU858
3.245
LYS860
3.775
PDB ID: 7K1I      EGFR kinase (L858R/V948R) in complex with allosteric inhibitor JBJ-09-063
Method X-ray diffraction Resolution 3.20 Å Mutation Yes [2]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPKANKEI
759
LDEAYVMASV
769
DNPHVCRLLG
779
ICLTSTVQLI
789
TQLMPFGCLL
799

DYVREHKDNI
809
GSQYLLNWCV
819
QIAKGMNYLE
829
DRRLVHRDLA
839
ARNVLVKTPQ
849

HVKITDFGRV
876
PIKWMALESI
886
IYTHQSDVWS
899
YGVTVWELMT
909
FGSKPYDGIP
919

ASEISSILEK
929
GERLPQPPIC
939
TIDVYMIMRK
949
CWMIDADSRP
959
KFRELIIEFS
969

KMARDPQRYL
979
VIQGDERMHL
989
PSPTDSNFYR
999
ALMDEEDM
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .VNS or .VNS2 or .VNS3 or :3VNS;style chemicals stick;color identity;select .A:726 or .A:743 or .A:744 or .A:745 or .A:747 or .A:749 or .A:755 or .A:758 or .A:759 or .A:762 or .A:763 or .A:766 or .A:775 or .A:776 or .A:777 or .A:788 or .A:789 or .A:790 or .A:854 or .A:855 or .A:856 or .A:857 or .A:858; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
VAL726
3.749
ALA743
3.289
ILE744
3.368
LYS745
3.028
LEU747
4.010
GLU749
4.880
ALA755
4.245
GLU758
4.271
ILE759
3.539
GLU762
3.612
ALA763
4.176
MET766
3.372
Residue
Distance (Å)
CYS775
3.401
ARG776
3.142
LEU777
3.108
LEU788
3.206
ILE789
4.095
THR790
3.364
THR854
4.071
ASP855
2.868
PHE856
2.601
GLY857
4.847
ARG858
3.246
References  Top
REF 1 An allosteric inhibitor against the therapy-resistant mutant forms of EGFR in non-small cell lung cancer. Nat Cancer. 2022 Apr;3(4):402-417.
REF 2 Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors. doi:10.1038/s41467-022-30258-y.
REF 3 Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors. Nat Commun. 2022 May 9;13(1):2530.

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