epidermal growth factor receptor | Type I RTKs: ErbB (epidermal growth factor) receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

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epidermal growth factor receptor

Target not currently curated in GtoImmuPdb

Target id: 1797

Nomenclature: epidermal growth factor receptor

Abbreviated Name: EGFR

Family: Type I RTKs: ErbB (epidermal growth factor) receptor family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1210 7p12 EGFR epidermal growth factor receptor
Mouse 1 1210 11 A1-A4 Egfr epidermal growth factor receptor
Rat - 1209 14q22 Egfr epidermal growth factor receptor
Previous and Unofficial Names
HER1 | avian erythroblastic leukemia viral (v-erbB) oncogene homolog | Wa5 | ERBB1
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  EGFR kinase domain complexed with a quinazoline inhibitor- GW572016
PDB Id:  1XKK
Ligand:  lapatinib
Resolution:  2.4Å
Species:  Human
References:  79
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains.
PDB Id:  1IVO
Resolution:  3.3Å
Species:  Human
References:  52
Enzyme Reaction
EC Number: 2.7.10.1
Natural/Endogenous Ligands
amphiregulin {Sp: Human}
betacellulin {Sp: Human}
EGF {Sp: Human}
epigen {Sp: Human}
epiregulin {Sp: Human}
HB-EGF {Sp: Human}
TGFα {Sp: Human}

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
canertinib Hs Inhibition 9.7 pKd 19
pKd 9.7 (Kd 1.9x10-10 M) [19]
afatinib Hs Inhibition 9.6 pKd 19
pKd 9.6 (Kd 2.5x10-10 M) [19]
erlotinib Hs Inhibition 9.2 pKd 19
pKd 9.2 (Kd 6.7x10-10 M) [19]
gefitinib Hs Inhibition 9.0 – 9.0 pKd 16,19
pKd 9.0 (Kd 1x10-9 M) [19]
pKd 9.0 (Kd 1.1x10-9 M) [16]
MS154 Hs Inhibition 8.7 pKd 16
pKd 8.7 (Kd 1.8x10-9 M) [16]
Description: Dissociation constant determined for wild type EGFR in a competitive binding assay.
MS39 Hs Inhibition 8.0 pKd 16
pKd 8.0 (Kd 1.1x10-8 M) [16]
Description: Dissociation constant determined for wild type EGFR in a competitive binding assay.
WZ4002 Hs Inhibition 7.3 pKd 85
pKd 7.3 (Kd 4.6x10-8 M) [85]
xiliertinib Hs Inhibition 10.3 pKi 61
pKi 10.3 (Ki 5x10-11 M) [61]
gefitinib Hs Inhibition 8.3 pKi 76
pKi 8.3 (Ki 5.5x10-9 M) [76]
PD166285 Hs Inhibition 7.1 pKi 53
pKi 7.1 (Ki 8.75x10-8 M) [53]
rociletinib Hs Inhibition 6.5 pKi 74
pKi 6.5 (Ki 3.033x10-7 M) [74]
AG 9 Hs Inhibition <3.4 pKi 27
pKi <3.4 (Ki >4x10-4 M) [27]
Description: Measuring phosphorylation of the EGFR exogenous substrate polyGAT [poly(Glu6Ala3Tyr)]
compound 56 [PMID: 8568816] Hs Inhibition 11.2 pIC50 9
pIC50 11.2 (IC50 6x10-12 M) [9]
BPIQ-I Hs Inhibition 10.6 pIC50 63
pIC50 10.6 (IC50 2.5x10-11 M) [63]
EGFR/ErbB-2/ErbB-4 inhibitor Hs Inhibition 9.5 pIC50 41
pIC50 9.5 (IC50 3x10-10 M) [41]
tesevatinib Hs Inhibition 9.5 pIC50 28
pIC50 9.5 (IC50 3x10-10 M) [28]
PD 174265 Hs Inhibition 9.4 pIC50 23
pIC50 9.4 (IC50 4.5x10-10 M) [23]
allitinib Hs Inhibition 9.3 pIC50 80
pIC50 9.3 (IC50 5x10-10 M) [80]
erlotinib Hs Inhibition 9.0 pIC50 84
pIC50 9.0 (IC50 1x10-9 M) [84]
nazartinib Hs Inhibition >9.0 pIC50 48
pIC50 >9.0 (IC50 <1x10-9 M) [48]
Description: Biochemical assay using EGFR L858R/T790M with a 90 minute preincubation with the inhibitor.
zorifertinib Hs Inhibition 8.1 – 9.5 pIC50 82
pIC50 9.5 (IC50 3x10-10 M) [82]
Description: Inhibition of wild type EGFR in vitro, at Km of ATP.
pIC50 8.1 (IC50 7.2x10-9 M) [82]
Description: Inhibition of EGFRL858R in vitro.
canertinib Hs Inhibition 8.8 pIC50 66
pIC50 8.8 (IC50 1.5x10-9 M) [66]
Description: Inhibition of kinase activity
AEE788 Hs Inhibition 8.7 pIC50 70
pIC50 8.7 (IC50 2x10-9 M) [70]
afatinib Hs Inhibition 8.0 – 9.3 pIC50 18,43
pIC50 8.0 – 9.3 (IC50 1.1x10-8 – 5x10-10 M) [18,43]
CUDC-101 Hs Inhibition 8.6 pIC50 11
pIC50 8.6 (IC50 2.4x10-9 M) [11]
pelitinib Hs Inhibition 7.8 – 9.2 pIC50 76-77
pIC50 7.8 – 9.2 (IC50 1.45x10-8 – 6x10-10 M) [76-77]
falnidamol Hs Inhibition 8.5 pIC50 67
pIC50 8.5 (IC50 3x10-9 M) [67]
PKI166 Hs Inhibition 8.4 pIC50 38
pIC50 8.4 (IC50 3.7x10-9 M) [38]
JAK3 inhibitor II Hs Inhibition 8.4 pIC50 15
pIC50 8.4 (IC50 4x10-9 M) [15]
sapitinib Hs Inhibition 8.4 pIC50 8
pIC50 8.4 (IC50 4x10-9 M) [8]
BMS-690514 Hs Inhibition 8.3 pIC50 49
pIC50 8.3 (IC50 5x10-9 M) [49]
ibrutinib Hs Inhibition 8.3 pIC50 10
pIC50 8.3 (IC50 5.3x10-9 M) [10]
AG1478 Hs Inhibition 8.2 pIC50 71
pIC50 8.2 (IC50 6x10-9 M) [71]
dacomitinib Hs Inhibition 8.2 pIC50 7
pIC50 8.2 (IC50 6x10-9 M) [7]
compound 38 [PMID: 24915291] Hs Inhibition 8.1 pIC50 45
pIC50 8.1 (IC50 7x10-9 M) [45]
abivertinib Hs Inhibition 8.1 pIC50 81
pIC50 8.1 (IC50 7.68x10-9 M) [81]
Description: In a biochemical assay.
poziotinib Hs Inhibition 8.1 pIC50 51
pIC50 8.1 (IC50 8x10-9 M) [51]
lapatinib Hs Inhibition 8.0 pIC50 65
pIC50 8.0 (IC50 1.02x10-8 M) [65]
ZM-306416 Hs Inhibition 8.0 pIC50 3
pIC50 8.0 (IC50 1x10-8 M) [3]
pyrotinib Hs Irreversible inhibition 7.9 pIC50 44
pIC50 7.9 (IC50 1.3x10-8 M) [44]
selatinib Hs Inhibition 7.9 pIC50 83
pIC50 7.9 (IC50 1.3x10-8 M) [83]
PD 158780 Hs Inhibition 7.8 pIC50 62
pIC50 7.8 (IC50 1.5x10-8 M) [62]
Description: Inhibition of EGFR autophosphorylation
EGFR/ErbB-2 inhibitor Hs Inhibition 7.7 pIC50 17
pIC50 7.7 (IC50 2x10-8 M) [17]
lazertinib Hs Inhibition >7.7 pIC50 68
pIC50 >7.7 (IC50 <2x10-8 M) [68]
Description: Measuring inhibition of mutant EGFR kinase activities in biochemical assays (equivalent potency against Del19, L858R, L858R/T790M and Del19/T790M EGFR mutants). NOTE lazertinib is inactive vs. wild type EGFR.
EGFR inhibitor Hs Inhibition 7.7 pIC50 21
pIC50 7.7 (IC50 2.1x10-8 M) [21]
lifirafenib Hs Inhibition 7.5 pIC50 69
pIC50 7.5 (IC50 2.9x10-8 M) [69]
Description: Inhibition of wild type EGFR kinase domain (aa669-1210)
compound 6g [PMID: 30633509] Hs Inhibition 7.5 pIC50 64
pIC50 7.5 (IC50 3x10-8 M) [64]
BMS-599626 Hs Inhibition 7.5 pIC50 25
pIC50 7.5 (IC50 3.2x10-8 M) [25]
icotinib Hs Inhibition 7.3 pIC50 33
pIC50 7.3 (IC50 4.5x10-8 M) [33]
Description: Inhibition of EGFR-mediated intracellular tyrosine phosphorylation in EGF-stimulated human A431 cells.
neratinib Hs Inhibition 7.0 pIC50 60
pIC50 7.0 (IC50 9.2x10-8 M) [60]
Description: Inhibition of autophosphorylation of the cytoplasmic domain of the RTK in a cell free system.
mobocertinib Hs Inhibition 7.0 pIC50 34
pIC50 7.0 (IC50 1x10-7 M) [34]
Description: Inhibition of EGFR harbouring concurring exon 21, L858R and T790M mutations.
AG 112 Hs Inhibition 6.9 pIC50 27
pIC50 6.9 (IC50 1.25x10-7 M) [27]
Description: Measuring inhibition of substrate phosphorylation.
brigatinib Hs Inhibition 6.9 pIC50 39
pIC50 6.9 (IC50 1.29x10-7 M) [39]
PF-670462 Hs Inhibition 6.8 pIC50 6
pIC50 6.8 (IC50 1.5x10-7 M) [6]
Description: In a biochemical kinase assay.
PP1 Hs Inhibition 6.6 pIC50 30
pIC50 6.6 (IC50 2.5x10-7 M) [30]
PP121 Hs Inhibition 6.6 pIC50 4
pIC50 6.6 (IC50 2.6x10-7 M) [4]
vandetanib Hs Inhibition 6.5 pIC50 13
pIC50 6.5 (IC50 3x10-7 M) [13]
mavelertinib Hs Inhibition 6.5 pIC50 58
pIC50 6.5 (IC50 3.07x10-7 M) [58]
olmutinib Hs Inhibition 6.0 – 7.0 pIC50 14
pIC50 6.0 – 7.0 (IC50 1x10-6 – 1x10-7 M) [14]
Description: Biochemical assay
AG 490 Hs Inhibition 6.4 pIC50 26
pIC50 6.4 (IC50 4x10-7 M) [26]
Description: Inhibition of substrate phosphorylation.
tucatinib Hs Inhibition 6.3 pIC50 42
pIC50 6.3 (IC50 4.49x10-7 M) [42]
Description: Inhibition of enzyme activity in a biochemical assay.
osimertinib Hs Inhibition 6.3 pIC50 75
pIC50 6.3 (IC50 4.94x10-7 M) [75]
compound 19a [PMID: 30503936] Hs Inhibition 6.3 pIC50 59
pIC50 6.3 (IC50 5.2x10-7 M) [59]
acalabrutinib Hs Inhibition <6.0 pIC50 10
pIC50 <6.0 (IC50 >1x10-6 M) [10]
dovitinib Hs Inhibition 5.7 pIC50 72
pIC50 5.7 (IC50 2x10-6 M) [72]
orantinib Hs Inhibition <4.0 pIC50 37
pIC50 <4.0 (IC50 >1x10-4 M) [37]
naquotinib Hs Inhibition - - 50
[50]
tarloxotinib Hs Inhibition - - 57
[57]
AST2818 Hs Inhibition - - 47
[47]
example 1 [WO2016094821A2] Hs Inhibition - - 56
[56]
Inhibitor Comments
AZD9291 is much more potent at mutant EGFRs, with IC50 values <100nM [5].
Note that the primary target of rociletinib, as a second-generation EGFR inhibitor, is mutant EGFR such as that with the gatekeeper T790M mutation [74].
Olmutinib potently inhibits EGFR in in vitro biochemical assay, but this does not translate to inhibition in vitro cellular assays [54].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
EAI045 Hs Inhibition - - 36
[36]
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
panitumumab Hs Antagonist 10.3 pKd 22
pKd 10.3 (Kd 5x10-11 M) [22]
necitumumab Hs Binding 9.5 pKd 46
pKd 9.5 (Kd 3.2x10-10 M) [46]
Description: Binding affinity of whole IMC-11F8 IgG using BIAcore sensor technology.
cetuximab Hs Binding 9.4 pKd 29
pKd 9.4 (Kd 3.9x10-10 M) [29]
JNJ-61186372 Hs Binding 8.9 pKd 35
pKd 8.9 (Kd 1.4x10-9 M) [35]
Description: Binding affinity determined by surface plasmon resonance.
MM-151 Hs Binding - - 31,40
[31,40]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
amphiregulin {Sp: Human} Hs Binding - -
betacellulin {Sp: Human} Hs Binding - -
EGF {Sp: Human} Hs Binding - -
epigen {Sp: Human} Hs Binding - -
epiregulin {Sp: Human} Hs Binding - -
HB-EGF {Sp: Human} Hs Binding - -
TGFα {Sp: Human} Hs Binding - -
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 19,78

Key to terms and symbols Click column headers to sort
Target used in screen: EGFR
Ligand Sp. Type Action Value Parameter
canertinib Hs Inhibitor Inhibition 9.7 pKd
afatinib Hs Inhibitor Inhibition 9.6 pKd
erlotinib Hs Inhibitor Inhibition 9.2 pKd
gefitinib Hs Inhibitor Inhibition 9.0 pKd
neratinib Hs Inhibitor Inhibition 9.0 pKd
lapatinib Hs Inhibitor Inhibition 8.6 pKd
vandetanib Hs Inhibitor Inhibition 8.0 pKd
bosutinib Hs Inhibitor Inhibition 7.5 pKd
dasatinib Hs Inhibitor Inhibition 6.9 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.7 pKd
Target used in screen: EGFR(E746-A750del)
Ligand Sp. Type Action Value Parameter
afatinib Hs Inhibitor Inhibition 10.0 pKd
canertinib Hs Inhibitor Inhibition 9.6 pKd
erlotinib Hs Inhibitor Inhibition 9.3 pKd
gefitinib Hs Inhibitor Inhibition 9.3 pKd
neratinib Hs Inhibitor Inhibition 8.6 pKd
vandetanib Hs Inhibitor Inhibition 8.3 pKd
lapatinib Hs Inhibitor Inhibition 8.1 pKd
bosutinib Hs Inhibitor Inhibition 7.7 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.1 pKd
staurosporine Hs Inhibitor Inhibition 6.9 pKd
Target used in screen: EGFR(G719C)
Ligand Sp. Type Action Value Parameter
afatinib Hs Inhibitor Inhibition 10.0 pKd
canertinib Hs Inhibitor Inhibition 9.9 pKd
neratinib Hs Inhibitor Inhibition 9.4 pKd
erlotinib Hs Inhibitor Inhibition 9.1 pKd
lapatinib Hs Inhibitor Inhibition 9.0 pKd
gefitinib Hs Inhibitor Inhibition 8.7 pKd
vandetanib Hs Inhibitor Inhibition 8.0 pKd
bosutinib Hs Inhibitor Inhibition 7.0 pKd
barasertib-hQPA Hs Inhibitor Inhibition 6.9 pKd
foretinib Hs Inhibitor Inhibition 6.9 pKd
Target used in screen: EGFR(G719S)
Ligand Sp. Type Action Value Parameter
afatinib Hs Inhibitor Inhibition 9.7 pKd
canertinib Hs Inhibitor Inhibition 9.7 pKd
erlotinib Hs Inhibitor Inhibition 9.3 pKd
neratinib Hs Inhibitor Inhibition 9.0 pKd
gefitinib Hs Inhibitor Inhibition 9.0 pKd
lapatinib Hs Inhibitor Inhibition 8.7 pKd
vandetanib Hs Inhibitor Inhibition 8.2 pKd
bosutinib Hs Inhibitor Inhibition 7.6 pKd
dasatinib Hs Inhibitor Inhibition 7.1 pKd
cediranib Hs Inhibitor Inhibition 7.1 pKd
Target used in screen: EGFR(L747-E749del, A750P)
Ligand Sp. Type Action Value Parameter
afatinib Hs Inhibitor Inhibition 9.9 pKd
canertinib Hs Inhibitor Inhibition 9.8 pKd
erlotinib Hs Inhibitor Inhibition 9.3 pKd
gefitinib