Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | (2R)-2-(5-fluoro-2-hydroxyphenyl)-2-{1-oxo-6-[4-(piperazin-1-yl)phenyl]-1,3-dihydro-2H-isoindol-2-yl}-N-(1,3-thiazol-2-yl)acetamide | Ligand Info | |||
| Canonical SMILES | C1CN(CCN1)C2=CC=C(C=C2)C3=CC4=C(CN(C4=O)C(C5=C(C=CC(=C5)F)O)C(=O)NC6=NC=CS6)C=C3 | ||||
| InChI | 1S/C29H26FN5O3S/c30-21-5-8-25(36)24(16-21)26(27(37)33-29-32-11-14-39-29)35-17-20-2-1-19(15-23(20)28(35)38)18-3-6-22(7-4-18)34-12-9-31-10-13-34/h1-8,11,14-16,26,31,36H,9-10,12-13,17H2,(H,32,33,37)/t26-/m1/s1 | ||||
| InChIKey | VHQVOTINPRYDAO-AREMUKBSSA-N | ||||
| PubChem Compound ID | 124173751 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 7JXP EGFR kinase (T790M/V948R) in complex with osimertinib and JBJ-04-125-02 | ||||||
| Method | X-ray diffraction | Resolution | 2.16 Å | Mutation | Yes | [1] |
| PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLA 859 KLVPIKWMAL883 ESILHRIYTH893 QSDVWSYGVT903 VWELMTFGSK913 PYDGIPASEI 923 SSILEKGERL933 PQPPICTIDV943 YMIMRKCWMI953 DADSRPKFRE963 LIIEFSKMAR 973 DPQRYLVIQG983 DERMHLPSPT993 DSNFYRALMD1003 EEDM
|
|||||
|
|
VAL726
3.688
ALA743
3.369
ILE744
3.504
LYS745
3.158
LEU747
3.300
THR751
4.385
ALA755
3.961
GLU758
3.356
ILE759
3.414
GLU762
3.331
ALA763
4.568
MET766
3.540
|
|||||
| PDB ID: 6DUK EGFR with an allosteric inhibitor | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [2] |
| PDB Sequence |
QALLRILKET
710 EFKKIKVLGS720 GAFGTVYKGL730 WIPEGEKVKI740 PVAIKELREA750 TSPKANKEIL 760 DEAYVMASVD770 NPHVCRLLGI780 CLTSTVQLIM790 QLMPFGCLLD800 YVREHKDNIG 810 SQYLLNWCVQ820 IAKGMNYLED830 RRLVHRDLAA840 RNVLVKTPQH850 VKITDFGLAK 860 LLGAEEKEYH870 AEGGKVPIKW880 MALESILHRI890 YTHQSDVWSY900 GVTVWELMTF 910 GSKPYDGIPA920 SEISSILEKG930 ERLPQPPICT940 IDVYMIMRKC950 WMIDADSRPK 960 FRELIIEFSK970 MARDPQRYLV980 IQGDERMHLP990 SPTDSNFYRA1000 LMDEED |
|||||
|
|
PHE723
3.583
VAL726
3.744
ALA743
3.540
ILE744
3.639
LYS745
3.249
LEU747
3.538
GLU749
2.736
THR751
4.313
ILE759
3.685
MET766
3.654
CYS775
3.541
ARG776
2.868
LEU777
2.948
|
|||||
| PDB ID: 7JXK EGFR kinase (T790M/V948R) in complex with PF-06747775 and JBJ-04-125-02 | ||||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [1] |
| PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLA 859 KLVPIKWMAL883 ESILHRIYTH893 QSDVWSYGVT903 VWELMTFGSK913 PYDGIPASEI 923 SSILEKGERL933 PQPPICTIDV943 YMIMRKCWMI953 DADSRPKFRE963 LIIEFSKMAR 973 DPQRYLVIQG983 DERMHLPSPT993 DSNFYRALMD1003 EEDM
|
|||||
|
|
VAL726
3.769
ALA743
3.179
ILE744
3.502
LYS745
3.208
LEU747
3.834
THR751
4.389
ALA755
3.746
GLU758
3.424
ILE759
3.700
GLU762
3.488
ALA763
4.038
MET766
3.472
CYS775
3.347
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors. doi:10.1038/s41467-022-30258-y. | ||||
| REF 2 | Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor. Cancer Discov. 2019 Jul;9(7):926-943. | ||||
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