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 | 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 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLA 859 KLLKVPIKWM881 ALESILHRIY891 THQSDVWSYG901 VTVWELMTFG911 SKPYDGIPAS 921 EISSILEKGE931 RLPQPPICTI941 DVYMIMRKCW951 MIDADSRPKF961 RELIIEFSKM 971 ARDPQRYLVI981 Q
|
|||||
|
|
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
|
|||||
| PDB ID: 7LGS Structure of EGFR_D770_N771insNPG/V948R in complex with covalent inhibitor Osimertinib. | ||||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [2] |
| PDB Sequence |
ALLRILKETE
711 FKKIKVLGSG721 AFGTVYKGLW731 IPKVKIPVAI744 KELREATSPK754 ANKEILDEAY 764 VMASVDNPGN774 PHVCRLLGIC784 LTSTVQLITQ794 LMPFGCLLDY804 VREHKDNIGS 814 QYLLNWCVQI824 AKGMNYLEDR834 RLVHRDLAAR844 NVLVKTPQHV854 KITDFGLAKL 864 LGAEEKEYHA874 EGGKVPIKWM884 ALESILHRIY894 THQSDVWSYG904 VTVWELMTFG 914 SKPYDGIPAS924 EISSILEKGE934 RLPQPPICTI944 DVYMIMRKCW954 MIDADSRPKF 964 RELIIEFSKM974 ARDPQRYLVI984 QGD
|
|||||
|
|
LEU718
3.154
GLY719
3.630
PHE723
4.224
VAL726
3.534
ALA743
3.893
LYS745
4.523
THR793
4.541
GLN794
3.959
LEU795
3.474
MET796
3.020
PRO797
3.345
|
|||||
| PDB ID: 6XL4 EGFR(T790M/V948R) in complex with AZD9291 and DDC4002 | ||||||
| Method | X-ray diffraction | Resolution | 2.06 Å | Mutation | Yes | [3] |
| PDB Sequence |
NQALLRILKE
709 TEFKKIKVLG719 SGAFGTVYKG729 LWIPEGEKVK739 IPVAIKELRE749 ATSPKANKEI 759 LDEAYVMASV769 DNPHVCRLLG779 ICLTSTVQLI789 MQLMPFGCLL799 DYVREHKDNI 809 GSQYLLNWCV819 QIAKGMNYLE829 DRRLVHRDLA839 ARNVLVKTPQ849 HVKITDFGLA 859 KVPIKWMALE884 SILHRIYTHQ894 SDVWSYGVTV904 WELMTFGSKP914 YDGIPASEIS 924 SILEKGERLP934 QPPICTIDVY944 MIMRKCWMID954 ADSRPKFREL964 IIEFSKMARD 974 PQRYLVIQGD984 ERMHLPSPTD994 SNFYRALMDE1004 EDM
|
|||||
|
|
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
|
|||||
| 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 | Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non-Small Cell Lung Cancer. Cancer Discov. 2021 Feb 25;candisc.1683.2020. | ||||
| REF 3 | 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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