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-[7-methyl-1-[(3R)-1-propanoylazepan-3-yl]benzimidazol-2-yl]-3-(trifluoromethyl)benzamide Ligand Info
Canonical SMILES CCC(=O)N1CCCCC(C1)N2C3=C(C=CC=C3N=C2NC(=O)C4=CC(=CC=C4)C(F)(F)F)C
InChI 1S/C25H27F3N4O2/c1-3-21(33)31-13-5-4-11-19(15-31)32-22-16(2)8-6-12-20(22)29-24(32)30-23(34)17-9-7-10-18(14-17)25(26,27)28/h6-10,12,14,19H,3-5,11,13,15H2,1-2H3,(H,29,30,34)/t19-/m1/s1
InChIKey DFNLNAPTJYVZSV-LJQANCHMSA-N
PubChem Compound ID 137348410
Drug Binding Sites of Target  Top
PDB ID: 5FED      EGFR kinase domain in complex with a covalent aminobenzimidazole inhibitor.
Method X-ray diffraction Resolution 2.65 Å Mutation No [1]
PDB Sequence
EAPNQALLRI
706
LKETEFKKIK
716
VLGSGTVYKG
729
LWIPEGEKVK
739
IPVAIKESPK
754

ANKEILDEAY
764
VMASVDNPHV
774
CRLLGICLTS
784
TVQLITQLMP
794
FGCLLDYVRE
804

HKDNIGSQYL
814
LNWCVQIAKG
824
MNYLEDRRLV
834
HRDLAARNVL
844
VKTPQHVKIT
854

DFGLAKLLKE
868
YHAEGGKVPI
878
KWMALESILH
888
RIYTHQSDVW
898
SYGVTVWELM
908

TFGSKPYDGI
918
PASEISSILE
928
KGERLPQPPI
938
CTIDVYMIMV
948
KCWMIDADSR
958

PKFRELIIEF
968
SKMARDPQRY
978
LVIQGDEMDD
1009
VVDADEYL
Residue
Distance (Å)
LEU718
3.587
GLY719
4.240
VAL726
3.328
ALA743
3.461
LYS745
3.004
CYS775
3.788
THR790
2.896
GLN791
3.359
LEU792
3.681
MET793
2.880
Residue
Distance (Å)
PRO794
2.983
PHE795
4.284
GLY796
3.672
CYS797
1.833
ASP800
3.369
ARG841
4.307
LEU844
3.526
THR854
3.466
ASP855
4.942
PDB ID: 5FEE      EGFR kinase domain T790M mutant in complex with a covalent aminobenzimidazole inhibitor.
Method X-ray diffraction Resolution 2.70 Å Mutation Yes [1]
PDB Sequence
EAPNQALLRI
706
LKETEFKKIK
716
VLGSTVYKGL
730
WIPEGEKVKI
740
PVAIKESPKA
755

NKEILDEAYV
765
MASVDNPHVC
775
RLLGICLTST
785
VQLIMQLMPF
795
GCLLDYVREH
805

KDNIGSQYLL
815
NWCVQIAKGM
825
NYLEDRRLVH
835
RDLAARNVLV
845
KTPQHVKITD
855

FGLAKLLEYH
870
AEGGKVPIKW
880
MALESILHRI
890
YTHQSDVWSY
900
GVTVWELMTF
910

GSKPYDGIPA
920
SEISSILEKG
930
ERLPQPPICT
940
IDVYMIMVKC
950
WMIDADSRPK
960

FRELIIEFSK
970
MARDPQRYLV
980
IQGDEMDDVV
1011
DADEYLI
Residue
Distance (Å)
LEU718
3.819
GLY719
4.187
VAL726
3.575
ALA743
3.535
LYS745
3.231
CYS775
3.595
MET790
3.576
GLN791
3.273
LEU792
3.712
MET793
2.928
Residue
Distance (Å)
PRO794
3.024
PHE795
4.389
GLY796
3.706
CYS797
1.835
ASP800
3.659
ARG841
3.778
LEU844
3.728
THR854
3.481
ASP855
4.477
References  Top
REF 1 Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T790M) EGFR Mutants for the Treatment of EGFR Mutant Non-Small-Cell Lung Cancers. J Med Chem. 2016 Jul 28;59(14):6671-89.

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