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 TAK-285 Ligand Info
Canonical SMILES CC(C)(CC(=O)NCCN1C=CC2=C1C(=NC=N2)NC3=CC(=C(C=C3)OC4=CC=CC(=C4)C(F)(F)F)Cl)O
InChI 1S/C26H25ClF3N5O3/c1-25(2,37)14-22(36)31-9-11-35-10-8-20-23(35)24(33-15-32-20)34-17-6-7-21(19(27)13-17)38-18-5-3-4-16(12-18)26(28,29)30/h3-8,10,12-13,15,37H,9,11,14H2,1-2H3,(H,31,36)(H,32,33,34)
InChIKey ZYQXEVJIFYIBHZ-UHFFFAOYSA-N
PubChem Compound ID 11620908
Drug Binding Sites of Target  Top
PDB ID: 3W2O      EGFR Kinase domain T790M/L858R Mutant with TAK-285
Method X-ray diffraction Resolution 2.35 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
MHLPMDDVVD
1012

ADEYL
Residue
Distance (Å)
LEU718
3.967
GLY719
3.700
SER720
3.538
GLY721
3.624
PHE723
4.218
VAL726
3.788
ALA743
3.360
ILE744
4.056
LYS745
3.408
LEU747
4.093
ILE759
3.340
GLU762
3.163
Residue
Distance (Å)
ALA763
4.739
MET766
3.695
LEU788
3.165
ILE789
4.518
MET790
3.559
GLN791
3.407
LEU792
4.030
MET793
3.035
PRO794
4.966
GLY796
4.154
LEU844
4.067
PDB ID: 3POZ      EGFR Kinase domain complexed with tak-285
Method X-ray diffraction Resolution 1.50 Å Mutation No [2]
PDB Sequence
QALLRILKET
710
EFKKIKVLGS
720
GAFGTVYKGL
730
WIPVKIPVAI
744
KELANKEILD
761

EAYVMASVDN
771
PHVCRLLGIC
781
LTSTVQLITQ
791
LMPFGCLLDY
801
VREHKDNIGS
811

QYLLNWCVQI
821
AKGMNYLEDR
831
RLVHRDLAAR
841
NVLVKTPQHV
851
KITDFGLAKL
861

LGAEEKKVPI
878
KWMALESILH
888
RIYTHQSDVW
898
SYGVTVWELM
908
TFGSKPYDGI
918

PASEISSILE
928
KGERLPQPPI
938
CTIDVYMIMV
948
KCWMIDADSR
958
PKFRELIIEF
968

SKMARDPQRY
978
LVIQGDERMH
988
LPSPTDSNFY
998
RALMDVVDAD
1014
EYL
Residue
Distance (Å)
LEU718
3.936
GLY719
4.487
VAL726
3.470
ALA743
3.346
ILE744
4.445
LYS745
3.397
MET766
3.356
CYS775
3.181
ARG776
3.447
LEU777
3.287
LEU788
3.230
ILE789
4.423
THR790
3.474
GLN791
3.318
Residue
Distance (Å)
LEU792
3.813
MET793
2.963
GLY796
3.963
CYS797
4.597
ARG841
3.327
ASN842
3.549
LEU844
3.365
ILE853
4.103
THR854
3.259
ASP855
3.435
PHE856
2.852
LEU858
3.935
LEU1001
4.927
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 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.

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