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 N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]propanamide Ligand Info
Canonical SMILES CCC(=O)NC1=CC(=C(C=C1N(C)CCN(C)C)OC)NC2=NC=CC(=N2)C3=CN(C4=CC=CC=C43)C
InChI 1S/C28H35N7O2/c1-7-27(36)30-22-16-23(26(37-6)17-25(22)34(4)15-14-33(2)3)32-28-29-13-12-21(31-28)20-18-35(5)24-11-9-8-10-19(20)24/h8-13,16-18H,7,14-15H2,1-6H3,(H,30,36)(H,29,31,32)
InChIKey UHTBXBRYOKJTAN-UHFFFAOYSA-N
PubChem Compound ID 71244256
Drug Binding Sites of Target  Top
PDB ID: 6Z4B      Crystal Structure of EGFR-T790M/V948R in Complex with Osimertinib and EAI045
Method X-ray diffraction Resolution 2.50 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
KLLKVPIKWM
881
ALESILHRIY
891
THQSDVWSYG
901
VTVWELMTFG
911

SKPYDGIPAS
921
EISSILEKGE
931
RLPQPPICTI
941
DVYMIMRKCW
951
MIDADSRPKF
961

RELIIEFSKM
971
ARDPQRYLVI
981
Q
Residue
Distance (Å)
VAL717
4.205
LEU718
3.015
GLY719
3.491
SER720
3.871
GLY721
4.423
VAL726
3.456
ALA743
3.467
LYS745
4.402
MET790
3.576
GLN791
3.720
LEU792
3.645
MET793
3.224
Residue
Distance (Å)
PRO794
3.221
PHE795
4.817
GLY796
3.337
CYS797
1.822
LEU799
4.944
ASP800
3.378
ARG841
3.991
ASN842
4.792
LEU844
3.501
THR854
4.810
ASP855
2.961
PDB ID: 6XL4      EGFR(T790M/V948R) in complex with AZD9291 and DDC4002
Method X-ray diffraction Resolution 2.06 Å Mutation Yes [2]
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
KVPIKWMALE
884
SILHRIYTHQ
894
SDVWSYGVTV
904
WELMTFGSKP
914

YDGIPASEIS
924
SILEKGERLP
934
QPPICTIDVY
944
MIMRKCWMID
954
ADSRPKFREL
964

IIEFSKMARD
974
PQRYLVIQGD
984
ERMHLPSPTD
994
SNFYRALMDE
1004
EDM
Residue
Distance (Å)
LEU718
3.347
GLY719
3.948
PHE723
3.812
VAL726
3.530
ALA743
3.492
LYS745
4.908
MET790
3.492
GLN791
3.135
LEU792
3.606
MET793
2.633
Residue
Distance (Å)
PRO794
3.680
PHE795
4.869
GLY796
3.337
CYS797
1.766
LEU799
4.851
ASP800
3.232
GLU804
3.069
ARG841
3.650
LEU844
3.619
ASP855
3.621
References  Top
REF 1 Complex Crystal Structures of EGFR with Third-Generation Kinase Inhibitors and Simultaneously Bound Allosteric Ligands. ACS Med Chem Lett. 2020 Nov 5;11(12):2484-2490.
REF 2 Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors. Nat Commun. 2022 May 9;13(1):2530.

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