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 T16538 Target Info
Target Name EGFR T790M mutant (EGFR T790M)
Synonyms Receptor tyrosine-protein kinase erbB-1 T790M mutant; Proto-oncogene c-ErbB-1 T790M mutant; HER1 T790M mutant; Epidermal growth factor receptor T790M mutant; ERBB1 T790M mutant; ERBB T790M mutant
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
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.

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