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 4-(4-{[2-{[(3s)-1-Acetylpyrrolidin-3-Yl]amino}-9-(Propan-2-Yl)-9h-Purin-6-Yl]amino}phenyl)-1-Methylpiperazin-1-Ium Ligand Info
Canonical SMILES CC(C)N1C=NC2=C(N=C(N=C21)NC3CCN(C3)C(=O)C)NC4=CC=C(C=C4)N5CCN(CC5)C
InChI 1S/C25H35N9O/c1-17(2)34-16-26-22-23(27-19-5-7-21(8-6-19)32-13-11-31(4)12-14-32)29-25(30-24(22)34)28-20-9-10-33(15-20)18(3)35/h5-8,16-17,20H,9-15H2,1-4H3,(H2,27,28,29,30)/t20-/m0/s1
InChIKey ACTNABQUCQIOKX-FQEVSTJZSA-N
PubChem Compound ID 124222449
Drug Binding Sites of Target  Top
PDB ID: 5UGA      Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with 4-(4-{[2-{[(3S)-1-acetylpyrrolidin-3-yl]amino}-9-(propan-2-yl)-9H-purin-6-yl]amino}phenyl)-1-methylpiperazin-1-ium
Method X-ray diffraction Resolution 1.82 Å Mutation Yes [1]
PDB Sequence
LLRILKETEF
712
KKIKVLGSGA
722
FGTVYKGLWI
732
PEGEKVKIPV
742
AIKELREATS
752

PKANKEILDE
762
AYVMASVDNP
772
HVCRLLGICL
782
TSTVQLIMQL
792
MPFGCLLDYV
802

REHKDNIGSQ
812
YLLNWCVQIA
822
KGMNYLEDRR
832
LVHRDLAARN
842
VLVKTPQHVK
852

ITDFGRAKLL
862
GAEEKEYHAE
872
GGKVPIKWMA
882
LESILHRIYT
892
HQSDVWSYGV
902

TVWELMTFGS
912
KPYDGIPASE
922
ISSILEKGER
932
LPQPPICTID
942
VYMIMRKCWM
952

IDADSRPKFR
962
ELIIEFSKMA
972
RDPQRYLVIQ
982
GDE
Residue
Distance (Å)
LEU718
3.579
GLY719
3.695
SER720
3.688
PHE723
3.729
VAL726
3.357
ALA743
3.366
LYS745
4.043
CYS775
3.821
MET790
3.990
GLN791
3.125
LEU792
3.893
Residue
Distance (Å)
MET793
2.964
PRO794
3.226
PHE795
3.986
GLY796
3.313
CYS797
4.220
GLU804
4.816
ARG841
4.078
ASN842
3.611
LEU844
3.422
THR854
3.688
PHE856
3.787
PDB ID: 5UGB      Crystal structure of the EGFR kinase domain in complex with 4-(4-{[2-{[(3S)-1-acetylpyrrolidin-3-yl]amino}-9-(propan-2-yl)-9H-purin-6-yl]amino}phenyl)-1-methylpiperazin-1-ium
Method X-ray diffraction Resolution 2.53 Å Mutation No [1]
PDB Sequence
SGEAPNQALL
704
RILKETEFKK
714
IKVLGSGAFG
724
TVYKGLWIPE
734
GEKVKIPVAI
744

KELATSPKAN
756
KEILDEAYVM
766
ASVDNPHVCR
776
LLGICLTSTV
786
QLITQLMPFG
796

CLLDYVREHK
806
DNIGSQYLLN
816
WCVQIAKGMN
826
YLEDRRLVHR
836
DLAARNVLVK
846

TPQHVKITDF
856
GLAKLLGAEE
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
MHLPDMDDVV
1011

DADEYLI
Residue
Distance (Å)
LEU718
3.440
GLY719
4.438
PHE723
4.533
VAL726
3.940
ALA743
3.361
LYS745
4.631
CYS775
3.796
THR790
3.079
GLN791
3.128
LEU792
3.830
Residue
Distance (Å)
MET793
2.921
PRO794
3.070
PHE795
4.103
GLY796
3.459
CYS797
3.793
ASP800
4.861
GLU804
4.173
ARG841
4.646
LEU844
3.247
THR854
3.200
References  Top
REF 1 Discovery of N-((3R,4R)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR. J Med Chem. 2017 Apr 13;60(7):3002-3019.

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