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 N-(4-{[3-Chloro-4-(Pyridin-2-Ylmethoxy)phenyl]amino}-3-Cyano-7-Ethoxyquinolin-6-Yl)-4-(Dimethylamino)butanamide Ligand Info
Canonical SMILES CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)CCCN(C)C
InChI 1S/C30H31ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-6,8,10-12,14-16,18H,4,7,9,13,19H2,1-3H3,(H,34,35)(H,36,38)
InChIKey MIURWHKJMYMLCP-UHFFFAOYSA-N
PubChem Compound ID 44560357
Drug Binding Sites of Target  Top
PDB ID: 3W2Q      EGFR kinase domain T790M/L858R mutant with HKI-272
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [1]
PDB Sequence
HAPNQALLRI
706
LKETEFKKIK
716
VLGSGAFGTV
726
YKGLWIPEGE
736
KVKIPVAIKE
746

LREATSPKAN
756
KEILDEAYVM
766
ASVDNPHVCR
776
LLGICLTSTV
786
QLIMQLMPFG
796

CLLDYVREHK
806
DNIGSQYLLN
816
WCVQIAKGMN
826
YLEDRRLVHR
836
DLAARNVLVK
846

TPQHVKITDF
856
GRAKLLGAEE
866
KEYHAEGGKV
876
PIKWMALESI
886
LHRIYTHQSD
896

VWSYGVTVWE
906
LMTFGSKPYD
916
GIPASEISSI
926
LEKGERLPQP
936
PICTIDVYMI
946

MVKCWMIDAD
956
SRPKFRELII
966
EFSKMARDPQ
976
RYLVIQGDER
986
MHLPSPMDDV
1010

VDADEYL
Residue
Distance (Å)
LEU718
3.719
VAL726
4.136
ALA743
3.443
ILE744
4.209
LYS745
3.043
ILE759
3.172
GLU762
3.433
ALA763
3.716
MET766
3.593
LEU777
4.474
LEU788
3.640
MET790
3.156
Residue
Distance (Å)
GLN791
3.404
LEU792
3.838
MET793
2.992
PRO794
3.153
PHE795
4.297
GLY796
3.167
CYS797
1.864
LEU799
4.669
ASP800
3.372
ARG841
3.720
LEU844
3.564
THR854
4.444
PDB ID: 2JIV      Crystal structure of EGFR kinase domain T790M mutation in compex with HKI-272
Method X-ray diffraction Resolution 3.50 Å Mutation Yes [2]
PDB Sequence
NQALLRILKE
709
TEFKKIKVLG
719
SGAFGTVYKG
729
LWIPEGEKVK
739
IPVAIKELRE
749

ATSPANKEIL
760
DEAYVMASVD
770
NPHVCRLLGI
780
CLTSTVQLIM
790
QLMPFGCLLD
800

YVREHKDNIG
810
SQYLLNWCVQ
820
IAKGMNYLED
830
RRLVHRDLAA
840
RNVLVKTPQH
850

VKITDFGLAK
860
KVPIKWMALE
884
SILHRIYTHQ
894
SDVWSYGVTV
904
WELMTFGSKP
914

YDGIPASEIS
924
SILEKGERLP
934
QPPICTIDVY
944
MIMVKCWMID
954
ADSRPKFREL
964

IIEFSKMARD
974
PQRYLVIQGD
984
Residue
Distance (Å)
LEU718
3.710
GLY719
3.055
SER720
4.111
VAL726
4.404
ALA743
3.680
ILE744
3.192
LYS745
3.558
MET766
3.802
CYS775
4.210
ARG776
4.812
LEU777
3.884
LEU788
2.242
ILE789
3.870
MET790
2.921
Residue
Distance (Å)
GLN791
3.201
LEU792
3.339
MET793
3.204
PRO794
4.029
PHE795
3.893
GLY796
3.342
CYS797
1.826
ASP800
4.612
ARG841
4.333
LEU844
3.979
THR854
3.320
ASP855
3.522
PHE856
3.341
LEU858
4.389
References  Top
REF 1 Structure-Based Approach for the Discovery of Pyrrolo[3,2-d]pyrimidine-Based EGFR T790M/L858R Mutant Inhibitors. ACS Med Chem Lett. 2012 Dec 18;4(2):201-5.
REF 2 The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5.

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