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epidermal growth factor receptor

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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

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1210 7p11.2 EGFR epidermal growth factor receptor
Mouse 1 1210 11 9.41 cM Egfr epidermal growth factor receptor
Rat - 1209 14q22 Egfr epidermal growth factor receptor
Previous and Unofficial Names Click here for help
HER1 | avian erythroblastic leukemia viral (v-erbB) oncogene homolog | Wa5 | ERBB1
Database Links Click here for help
Alphafold P00533 (Hs), Q01279 (Mm)
BRENDA 2.7.10.1
CATH/Gene3D 3.80.20.20
ChEMBL Target CHEMBL203 (Hs), CHEMBL3608 (Mm)
DrugBank Target P00533 (Hs)
Ensembl Gene ENSG00000146648 (Hs), ENSMUSG00000020122 (Mm), ENSRNOG00000004332 (Rn)
Entrez Gene 1956 (Hs), 13649 (Mm), 24329 (Rn)
Human Protein Atlas ENSG00000146648 (Hs)
KEGG Enzyme 2.7.10.1
KEGG Gene hsa:1956 (Hs), mmu:13649 (Mm), rno:24329 (Rn)
OMIM 131550 (Hs)
Orphanet ORPHA121311 (Hs)
Pharos P00533 (Hs)
RefSeq Nucleotide NM_005228 (Hs), NM_207655 (Mm), NM_031507 (Rn)
RefSeq Protein NP_005219 (Hs), NP_997538 (Mm), NP_031938 (Mm), NP_113695 (Rn)
SynPHARM 80088 (in complex with AEE788)
79548 (in complex with afatinib)
79526 (in complex with erlotinib)
81179 (in complex with erlotinib)
81180 (in complex with gefitinib)
78743 (in complex with gefitinib)
80519 (in complex with PD 174265)
83611 (in complex with WZ4002)
UniProtKB P00533 (Hs), Q01279 (Mm)
Wikipedia EGFR (Hs)
Selected 3D Structures Click here for help
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:  102
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:  71
Enzyme Reaction Click here for help
EC Number: 2.7.10.1
Natural/Endogenous Ligands Click here for help
amphiregulin {Sp: Human}
betacellulin {Sp: Human}
EGF {Sp: Human}
epigen {Sp: Human}
epiregulin {Sp: Human}
HB-EGF {Sp: Human}
TGFα {Sp: Human}

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
canertinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.7 pKd 24
⤷ pKd 9.7 (Kd 1.9x10-10 M) [24]
afatinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.6 pKd 24
⤷ pKd 9.6 (Kd 2.5x10-10 M) [24]
erlotinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.2 pKd 24
⤷ pKd 9.2 (Kd 6.7x10-10 M) [24]
gefitinib Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.0 – 9.0 pKd 21,24
⤷ pKd 9.0 (Kd 1x10-9 M) [24]
pKd 9.0 (Kd 1.1x10-9 M) [21]
MS154 Small molecule or natural product Hs Inhibition 8.7 pKd 21
⤷ pKd 8.7 (Kd 1.8x10-9 M) [21]
Description: Dissociation constant determined for wild type EGFR in a competitive binding assay.
MS39 Small molecule or natural product Hs Inhibition 8.0 pKd 21
⤷ pKd 8.0 (Kd 1.1x10-8 M) [21]
Description: Dissociation constant determined for wild type EGFR in a competitive binding assay.
WZ4002 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pKd 112
⤷ pKd 7.3 (Kd 4.6x10-8 M) [112]
xiliertinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 10.3 pKi 80
⤷ pKi 10.3 (Ki 5x10-11 M) [80]
gefitinib Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.3 pKi 99
⤷ pKi 8.3 (Ki 5.5x10-9 M) [99]
PD166285 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 pKi 72
⤷ pKi 7.1 (Ki 8.75x10-8 M) [72]
rociletinib Small molecule or natural product Ligand has a PDB structure Hs Inhibition 6.5 pKi 95
⤷ pKi 6.5 (Ki 3.033x10-7 M) [95]
AG 9 Small molecule or natural product Primary target of this compound Hs Inhibition <3.4 pKi 34
⤷ pKi <3.4 (Ki >4x10-4 M) [34]
Description: Measuring phosphorylation of the EGFR exogenous substrate polyGAT [poly(Glu6Ala3Tyr)]
compound 56 [PMID: 8568816] Small molecule or natural product Primary target of this compound Hs Inhibition 11.2 pIC50 11
⤷ pIC50 11.2 (IC50 6x10-12 M) [11]
BPIQ-I Small molecule or natural product Primary target of this compound Hs Inhibition 10.6 pIC50 82
⤷ pIC50 10.6 (IC50 2.5x10-11 M) [82]
asandeutertinib Small molecule or natural product Hs Inhibition 8.6 – 10.9 pIC50 113
⤷ pIC50 10.9 (IC50 1.2x10-11 M) [113]
Description: Inhibition of phosphorylation of EGFR in NCI-H1975 cells with L858R/T790M EGFR double mutant
pIC50 10.7 (IC50 2x10-11 M) [113]
Description: Inhibition of phosphorylation of EGFR in PC9 cells with Exon19 deletion EGFR
pIC50 8.6 (IC50 2.53x10-9 M) [113]
Description: Inhibition of phosphorylation of WT EGFR in LoVo cells
TQB3804 Small molecule or natural product Hs Inhibition 9.7 – 9.8 pIC50 103
⤷ pIC50 9.8 (IC50 1.6x10-10 M) [103]
Description: Inhibition of EGFR L858R/T790M/C797S triple mutant
pIC50 9.7 (IC50 2.2x10-10 M) [103]
Description: Inhibition of EGFR Del19/T790M/C797S triple mutant
JBJ-04-125-02 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.6 pIC50 90
⤷ pIC50 9.6 (IC50 2.6x10-10 M) [90]
Description: Inhibition of EGFRL858R/T790M in a biochemical assay
CH7233163 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.6 pIC50 48
⤷ pIC50 9.6 (IC50 2.8x10-10 M) [48]
Description: Inhibition potency in a biochemical assay with EGFRDel19/T790M/C797S.
EGFR/ErbB-2/ErbB-4 inhibitor Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.5 pIC50 52
⤷ pIC50 9.5 (IC50 3x10-10 M) [52]
tesevatinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.5 pIC50 35
⤷ pIC50 9.5 (IC50 3x10-10 M) [35]
mifanertinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.4 pIC50 107
⤷ pIC50 9.4 (IC50 4x10-10 M) [107]
PD 174265 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.4 pIC50 30
⤷ pIC50 9.4 (IC50 4.5x10-10 M) [30]
allitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.3 pIC50 104
⤷ pIC50 9.3 (IC50 5x10-10 M) [104]
BI-4020 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.2 pIC50 25
⤷ pIC50 9.2 (IC50 6x10-10 M) [25]
Description: Inhibition od EGFR triple mutant del19/T790M/C797S in vitro
erlotinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 111
⤷ pIC50 9.0 (IC50 1x10-9 M) [111]
nazartinib Small molecule or natural product Hs Inhibition >9.0 pIC50 65
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [65]
Description: Biochemical assay using EGFR L858R/T790M with a 90 minute preincubation with the inhibitor.
pirotinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pIC50 43
⤷ pIC50 9.0 (IC50 1x10-9 M) [43]
zorifertinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 – 9.5 pIC50 109
⤷ pIC50 9.5 (IC50 3x10-10 M) [109]
Description: Inhibition of wild type EGFR in vitro, at Km of ATP.
pIC50 8.1 (IC50 7.2x10-9 M) [109]
Description: Inhibition of EGFRL858R in vitro.
canertinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.8 pIC50 85
⤷ pIC50 8.8 (IC50 1.5x10-9 M) [85]
Description: Inhibition of kinase activity
aumolertinib Small molecule or natural product Approved drug Hs Inhibition 8.7 pIC50 108
⤷ pIC50 8.7 (IC50 1.89x10-9 M) [108]
Description: Inhibition of wild type EGFR enzyme activity in a TR-FRET assay
AEE788 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.7 pIC50 91
⤷ pIC50 8.7 (IC50 2x10-9 M) [91]
afatinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 – 9.3 pIC50 23,55
⤷ pIC50 8.0 – 9.3 (IC50 1.1x10-8 – 5x10-10 M) [23,55]
CUDC-101 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.6 pIC50 13
⤷ pIC50 8.6 (IC50 2.4x10-9 M) [13]
compound 17b [PMID: 35286086] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.6 pIC50 1
⤷ pIC50 8.6 (IC50 2.5x10-9 M) [1]
pelitinib Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.8 – 9.2 pIC50 99-100
⤷ pIC50 7.8 – 9.2 (IC50 1.45x10-8 – 6x10-10 M) [99-100]
falnidamol Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 86
⤷ pIC50 8.5 (IC50 3x10-9 M) [86]
PKI166 Small molecule or natural product Hs Inhibition 8.4 pIC50 49
⤷ pIC50 8.4 (IC50 3.7x10-9 M) [49]
JAK3 inhibitor II Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.4 pIC50 18
⤷ pIC50 8.4 (IC50 4x10-9 M) [18]
sapitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pIC50 9
⤷ pIC50 8.4 (IC50 4x10-9 M) [9]
zipalertinib Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.1 – 8.7 pIC50 39
⤷ pIC50 8.7 (IC50 2x10-9 M) [39]
Description: Inhibition of hEGFR with T790M/L858R mutation in a biochemical enzyme assay
pIC50 8.1 (IC50 7.4x10-9 M) [39]
Description: Inhibition of hEGFR with D770_N771insNPG insertion in a biochemical enzyme assay
pIC50 8.1 (IC50 8x10-9 M) [39]
Description: Inhibition of WT hEGFR in a biochemical enzyme assay
BMS-690514 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.3 pIC50 66
⤷ pIC50 8.3 (IC50 5x10-9 M) [66]
ibrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 12
⤷ pIC50 8.3 (IC50 5.3x10-9 M) [12]
JND3229 Small molecule or natural product Hs Inhibition 8.2 pIC50 62
⤷ pIC50 8.2 (IC50 5.8x10-9 M) [62]
Description: Inhibition of EGFRdel19/T790M/C797S
AG1478 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.2 pIC50 92
⤷ pIC50 8.2 (IC50 6x10-9 M) [92]
dacomitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 8
⤷ pIC50 8.2 (IC50 6x10-9 M) [8]
compound 38 [PMID: 24915291] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 58
⤷ pIC50 8.1 (IC50 7x10-9 M) [58]
abivertinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 105
⤷ pIC50 8.1 (IC50 7.68x10-9 M) [105]
Description: In a biochemical assay.
poziotinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 69
⤷ pIC50 8.1 (IC50 8x10-9 M) [69]
example 10 [CN110740999A] Small molecule or natural product Hs Inhibition 6.4 – 9.7 pIC50 54
⤷ pIC50 9.7 (IC50 2x10-10 M) [54]
Description: Inhibition of EGFR with triple del19/T790M/C797S mutation in an enzymatic assay
pIC50 9.1 (IC50 7x10-10 M) [54]
Description: Inhibition of EGFR with del19 mutation in an enzymatic assay
pIC50 8.4 (IC50 4x10-9 M) [54]
Description: Inhibition of EGFR with dual del19/T790M mutation in an enzymatic assay
pIC50 6.4 (IC50 4.3x10-7 M) [54]
Description: Inhibition of WT EGFR in an enzymatic assay
lapatinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.0 pIC50 84
⤷ pIC50 8.0 (IC50 1.02x10-8 M) [84]
ZM-306416 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.0 pIC50 4
⤷ pIC50 8.0 (IC50 1x10-8 M) [4]
pyrotinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Irreversible inhibition 7.9 pIC50 57
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [57]
selatinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 110
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [110]
dosimertinib Small molecule or natural product Hs Inhibition 6.9 – 8.8 pIC50 68
⤷ pIC50 8.8 (IC50 1.7x10-9 M) [68]
Description: Enzymatic inhibitory activity vs. L858R/T790M EGFR
pIC50 6.9 (IC50 1.138x10-7 M) [68]
Description: Enzymatic inhibitory activity vs. WT EGFR
PD 158780 Small molecule or natural product Primary target of this compound Hs Inhibition 7.8 pIC50 81
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [81]
Description: Inhibition of EGFR autophosphorylation
tigozertinib Small molecule or natural product Hs Inhibition >7.8 pIC50 14
⤷ pIC50 >7.8 (IC50 <1.5x10-8 M) [14]
Description: Biochemical enzyme inhibition assay (measuring inhibition of peptide substrate phosphorylation) using EGFR with triple mutation (del 19 or exon 21 L858R substitution mutation, T790M mutation, and C797S mutation)
compound 18j [PMID: 35446588] Small molecule or natural product Hs Inhibition 7.6 – 7.8 pIC50 19
⤷ pIC50 7.8 (IC50 1.58x10-8 M) [19]
Description: Inhibition of EGFRdel19/T790M/C797S
pIC50 7.6 (IC50 2.36x10-8 M) [19]
Description: Inhibition of EGFR L858R/T790M/C797S mutant
compound 52 [PMID: 36749735] Small molecule or natural product Hs Inhibition 7.6 – 7.8 pIC50 56
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [56]
Description: Inhibition of EGFRL858R/T790M enzyme activity
pIC50 7.6 (IC50 2.5x10-8 M) [56]
Description: Inhibition of WT EGFR enzymatic activity
EGFR/ErbB-2 inhibitor Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.7 pIC50 22
⤷ pIC50 7.7 (IC50 2x10-8 M) [22]
lazertinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition >7.7 pIC50 87
⤷ pIC50 >7.7 (IC50 <2x10-8 M) [87]
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 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.7 pIC50 27
⤷ pIC50 7.7 (IC50 2.1x10-8 M) [27]
BDTX-1535 Small molecule or natural product Hs Inhibition >7.3 – 8.0 pIC50 63
⤷ pIC50 >8.0 (IC50 <1x10-8 M) [63]
Description: Inhibition of phosphorylation of EGFR with mutantions A289V and G598V
pIC50 7.6 – 8.0 (IC50 2.5x10-8 – 1x10-8 M) [63]
Description: Inhibition of hEGFRV3 (constitutively activated mutant) phosphorylation
pIC50 >7.3 – 7.6 (IC50 <5x10-8 – 2.5x10-8 M) [63]
Description: Inhibition of WT hEGFR phosphorylation
C34 [Zhu et al., 2023] Small molecule or natural product Hs Inhibition 7.0 – 8.3 pIC50 114
⤷ pIC50 8.3 (IC50 5.1x10-9 M) [114]
Description: Inhibition of EGFR triple mutant L858R/T790M/C797S
pIC50 7.0 (IC50 1.06x10-7 M) [114]
Description: Inhibition of wild type hEGFR
lifirafenib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 88
⤷ pIC50 7.5 (IC50 2.9x10-8 M) [88]
Description: Inhibition of wild type EGFR kinase domain (aa669-1210)
compound 6g [PMID: 30633509] Small molecule or natural product Hs Inhibition 7.5 pIC50 83
⤷ pIC50 7.5 (IC50 3x10-8 M) [83]
BMS-599626 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pIC50 32
⤷ pIC50 7.5 (IC50 3.2x10-8 M) [32]
AZ5104 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.5 pIC50 20
⤷ pIC50 7.5 (IC50 3.3x10-8 M) [20]
Description: Inhibition of wild type EGFR phosphorylation in human LoVo cells
EP26 Small molecule or natural product Hs Inhibition 7.4 pIC50 106
⤷ pIC50 7.4 (IC50 3.75x10-8 M) [106]
icotinib Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.3 pIC50 41
⤷ pIC50 7.3 (IC50 4.5x10-8 M) [41]
Description: Inhibition of EGFR-mediated intracellular tyrosine phosphorylation in EGF-stimulated human A431 cells.
DBPR112 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 7.3 pIC50 60
⤷ pIC50 7.3 (IC50 4.8x10-8 M) [60]
Description: Enzymatic activity inhibition of EGFRL858R/T790M
sunvozertinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.1 pIC50 59
⤷ pIC50 7.1 (IC50 8.04x10-8 M) [59]
Description: Inhibition of WT EGFR phosphorylation in A431 cells
neratinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.0 pIC50 79
⤷ pIC50 7.0 (IC50 9.2x10-8 M) [79]
Description: Inhibition of autophosphorylation of the cytoplasmic domain of the RTK in a cell free system.
mobocertinib Small molecule or natural product Approved drug Hs Inhibition 7.0 pIC50 42
⤷ pIC50 7.0 (IC50 1x10-7 M) [42]
Description: Inhibition of EGFR harbouring concurring exon 21, L858R and T790M mutations.
AG 112 Small molecule or natural product Primary target of this compound Hs Inhibition 6.9 pIC50 34
⤷ pIC50 6.9 (IC50 1.25x10-7 M) [34]
Description: Measuring inhibition of substrate phosphorylation.
brigatinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.9 pIC50 50
⤷ pIC50 6.9 (IC50 1.29x10-7 M) [50]
PF-670462 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 7
⤷ pIC50 6.8 (IC50 1.5x10-7 M) [7]
Description: In a biochemical kinase assay.
PP1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 37
⤷ pIC50 6.6 (IC50 2.5x10-7 M) [37]
ralimetinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.2 – 8.0 pIC50 10
⤷ pIC50 8.0 (IC50 1.1x10-8 M) [10]
Description: Inhibitor potency for EGFRG719C
pIC50 6.7 (IC50 1.8x10-7 M) [10]
Description: Inhibitor potency for WT EGFR
pIC50 5.2 (IC50 6.06x10-6 M) [10]
Description: Inhibitor potency for EGFR with gatekeeper mutation T790M
PP121 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pIC50 5
⤷ pIC50 6.6 (IC50 2.6x10-7 M) [5]
BI-4142 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pIC50 98
⤷ pIC50 6.6 (IC50 2.7x10-7 M) [98]
Description: Inhibition of autophosphorylation of WT EGFR overexpressed in HEK293 cells
vandetanib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.5 pIC50 16
⤷ pIC50 6.5 (IC50 3x10-7 M) [16]
mavelertinib Small molecule or natural product Hs Inhibition 6.5 pIC50 77
⤷ pIC50 6.5 (IC50 3.07x10-7 M) [77]
olmutinib Small molecule or natural product Approved drug Hs Inhibition 6.0 – 7.0 pIC50 17
⤷ pIC50 6.0 – 7.0 (IC50 1x10-6 – 1x10-7 M) [17]
Description: Biochemical assay
tuxobertinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 – 6.5 pIC50 28
⤷ pIC50 6.3 – 6.5 (IC50 5x10-7 – 3x10-7 M) [28]
Description: Inhibition of WT EGFR kinase activity
AG 490 Small molecule or natural product Primary target of this compound Hs Inhibition 6.4 pIC50 33
⤷ pIC50 6.4 (IC50 4x10-7 M) [33]
Description: Inhibition of substrate phosphorylation.
tucatinib Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.3 pIC50 53
⤷ pIC50 6.3 (IC50 4.49x10-7 M) [53]
Description: Inhibition of enzyme activity in a biochemical assay.
osimertinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibition 6.3 pIC50 96
⤷ pIC50 6.3 (IC50 4.94x10-7 M) [96]
compound 19a [PMID: 30503936] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pIC50 78
⤷ pIC50 6.3 (IC50 5.2x10-7 M) [78]
zongertinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 97
⤷ pIC50 6.2 (IC50 5.79x10-7 M) [97]
Description: Inhibition of wild type EGFR phosphorylation
acalabrutinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition <6.0 pIC50 12
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [12]
dovitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.7 pIC50 93
⤷ pIC50 5.7 (IC50 2x10-6 M) [93]
orantinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition <4.0 pIC50 47
⤷ pIC50 <4.0 (IC50 >1x10-4 M) [47]
naquotinib Small molecule or natural product Ligand has a PDB structure Hs Inhibition - - 67
⤷ [67]
tarloxotinib Small molecule or natural product Hs Inhibition - - 76
⤷ [76]
firmonertinib Small molecule or natural product Approved drug Hs Inhibition - - 64
⤷ [64]
rezivertinib Small molecule or natural product Hs Inhibition - - 75
⤷ [75]
befotertinib Small molecule or natural product Approved drug Hs Inhibition - - 46
⤷ [46]
Inhibitor Comments
AZD9291 is much more potent at mutant EGFRs, with IC50 values <100nM [6].
Note that the primary target of rociletinib, as a second-generation EGFR inhibitor, is mutant EGFR such as that with the gatekeeper T790M mutation [95].
Olmutinib potently inhibits EGFR in in vitro biochemical assay, but this does not translate to inhibition in vitro cellular assays [73].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
JBJ-09-063 Small molecule or natural product Hs Negative 10.1 pIC50 89
⤷ pIC50 10.1 (IC50 8.3x10-11 M) [89]
Description: Inhibition of enzyme activity of triple mutant EGFR L858R/T790M/C797S
EGFR inhibitor 57 Small molecule or natural product Hs Inhibition 7.7 – 8.7 pIC50 70
⤷ pIC50 8.7 (IC50 2x10-9 M) [70]
Description: Inhibition potency for EGFR with the L858R/T790M/C797S triple mutation.
pIC50 7.7 (IC50 2x10-8 M) [70]
Description: Inhibition potency for EGFR with the L858R/C797S double mutation
EAI045 Small molecule or natural product Hs Inhibition - - 45
⤷ [45]
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
panitumumab Peptide Approved drug Primary target of this compound Hs Antagonist 10.3 pKd 29
⤷ pKd 10.3 (Kd 5x10-11 M) [29]
necitumumab Peptide Approved drug Primary target of this compound Hs Binding 9.5 pKd 61
⤷ pKd 9.5 (Kd 3.2x10-10 M) [61]
Description: Binding affinity of whole IMC-11F8 IgG using BIAcore sensor technology.
cetuximab Peptide Approved drug Primary target of this compound Hs Binding 9.4 pKd 36
⤷ pKd 9.4 (Kd 3.9x10-10 M) [36]
amivantamab Peptide Approved drug Primary target of this compound Click here for species-specific activity table Hs Binding 8.9 pKd 44
⤷ pKd 8.9 (Kd 1.4x10-9 M) [44]
Description: Binding affinity determined by surface plasmon resonance.
MM-151 Peptide Primary target of this compound Hs Binding - - 38,51
⤷ [38,51]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
amphiregulin {Sp: Human} Peptide Ligand is endogenous in the given species Immunopharmacology Ligand Hs Binding - -
⤷
betacellulin {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Binding - -
⤷
EGF {Sp: Human} Peptide Ligand is endogenous in the given species Hs Binding - -
⤷
epigen {Sp: Human} Peptide Ligand is endogenous in the given species Hs Binding - -
⤷
epiregulin {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Binding - -
⤷
HB-EGF {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Binding - -
⤷
TGFα {Sp: Human} Peptide Ligand is endogenous in the given species Hs Binding - -
⤷
DiscoveRx KINOMEscan® screen Click here for help
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: 24,101
Key to terms and symbols Click column headers to sort
Target used in screen: EGFR
Ligand Sp. Type Action Value Parameter
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.7 pKd
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.6 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.2 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 9.0 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.9 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
Target used in screen: EGFR(E746-A750del)
Ligand Sp. Type Action Value Parameter
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 10.0 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.6 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 8.6 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.7 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
Target used in screen: EGFR(G719C)
Ligand Sp. Type Action Value Parameter
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 10.0 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.9 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 9.4 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
barasertib-hQPA Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
Target used in screen: EGFR(G719S)
Ligand Sp. Type Action Value Parameter
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.7 pKd
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.7 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 9.0 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.2 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.6 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
Target used in screen: EGFR(L747-E749del, A750P)
Ligand Sp. Type Action Value Parameter
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.9 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.8 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.2 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 9.2 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.7 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
Target used in screen: EGFR(L747-S752del, P753S)
Ligand Sp. Type Action Value Parameter
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.9 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.6 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.2 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 9.0 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.4 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
Target used in screen: EGFR(L747-T751del,Sins)
Ligand Sp. Type Action Value Parameter
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.9 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.6 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.5 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.3 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 9.0 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
Target used in screen: EGFR(L858R)
Ligand Sp. Type Action Value Parameter
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.7 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.6 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 9.2 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.6 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.6 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.3 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.9 pKd
Target used in screen: EGFR(L858R,T790M)
Ligand Sp. Type Action Value Parameter
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.5 pKd
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.1 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.1 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 7.6 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
GSK-1838705A Small molecule or natural product Hs Inhibitor Inhibition 6.8 pKd
Target used in screen: EGFR(L861Q)
Ligand Sp. Type Action Value Parameter
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.7 pKd
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.6 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 9.4 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.9 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
Target used in screen: EGFR(S752-I759del)
Ligand Sp. Type Action Value Parameter
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.9 pKd
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 9.7 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 9.2 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.8 pKd
lapatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 8.4 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
Target used in screen: EGFR(T790M)
Ligand Sp. Type Action Value Parameter
canertinib Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 10.0 pKd
afatinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.2 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 8.8 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.0 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
GSK-1838705A Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 3,31
Key to terms and symbols Click column headers to sort
Target used in screen: EGFR/EGFR
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
AG1478 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 0.7 -5.0 -3.0
EGFR/ErbB-2/ErbB-4 inhibitor Small molecule or natural product Hs Inhibitor Inhibition 1.2 -4.0 -3.0
compound 56 [PMID: 8568816] Small molecule or natural product Hs Inhibitor Inhibition 2.0 -5.0 -4.0
PD 158780 Small molecule or natural product Hs Inhibitor Inhibition 2.0 -2.0 -3.0
PD 174265 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.2 -3.0 -3.0
JAK3 inhibitor II Small molecule or natural product Hs Inhibitor Inhibition 2.2 -4.0 -3.0
gefitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 3.0
BPIQ-I Small molecule or natural product Hs Inhibitor Inhibition 3.6 -4.0 -3.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 3.8
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 4.2
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Barrier integrity
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Asthma
Description: A bronchial disease characterized by chronic inflammation and narrowing of the airways; caused by a combination of environmental and genetic factors.
Disease Ontology: DOID:2841
OMIM: 600807
Role:  Although EGFR signalling is an important pathway in bronchial epithelial repair, its dysregulation has been implicated in the pathogenesis of asthma (Holgate, 2000). Over-expression of EGFR and its ligands by airway epithelial cells have been seen in patients with asthma in relation to disease severity (Amishima et al., 1998; Enomoto et al., 2009). There is also evidence that the asthmatic airway epithelium challenged with EGF can enhance the production of pro-survival and pro-migratory factors for neutrophils that may contribute to airway mucosal inflammation in severe asthma (Uddin et al., 2013).
References:  2,26,40,94
Disease:  Giant cell glioblastoma
Synonyms: Glioma susceptibility 1; GLM1 [OMIM: 137800]
Disease Ontology: DOID:3074
OMIM: 137800
Orphanet: ORPHA251579
Disease:  Gliosarcoma
Disease Ontology: DOID:3071
Orphanet: ORPHA251576
Disease:  Inflammatory skin and bowel disease, neonatal, 2; NISBD2
Synonyms: Neonatal inflammatory skin and bowel disease [Orphanet: ORPHA294023]
OMIM: 616069
Orphanet: ORPHA294023
Comments:  A homozygous missense mutation in the EGFR gene has been reported in a single patient who died from neonatal inflammatory skin and bowel disease.
References:  15
Disease:  Lung cancer
Disease Ontology: DOID:1324
OMIM: 211980
Role:  Mutations in EGFR are associated with non-small cell lung cancer and adenocarcinoma of the lung.
Gene Expression and Pathophysiology Comments
EGFR mutations that are commonly found in tumours are the L858R receptor-activating mutation, and the T790M mutation that confers resistance to many early generation EGFR kinase inhibitors. Allosteric inhibitors such as EAI045 are being developed to combat the pathological effects of these mutations.
General Comments
The EGFR is a highly exploited molecular target for the treatment of EGF-driven solid tumours, with several inhibitors of this receptor tyrosine kinase already in the clinic. Next-generation tyrosine kinase inhibitors (TKIs) have been developed to overcome acquired tumour resistance to the founder drugs. Second and third-generation inhibitors have been developed and advanced to clinical trial. Third-generation inhibitors (e.g. osimertinib, rociletinib, olmutinib, naquotinib, nazartinib, and mavelertinib) are wild-type-sparing drugs that target for example, the T790M gatekeeper mutant EGFR (the most commonly identified cause of resistance to earlier generation TKIs). However, resistance to third generation agents has also been reported, and has been linked to the presence of an EGFRC797S mutation. Progress towards the development of fourth generation EGFR inhibitors to overcome C797S resistance is reviewed by Patel et al. (2017) [74].

References

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Type I RTKs: ErbB (epidermal growth factor) receptor family: epidermal growth factor receptor. Last modified on 16/05/2024. Accessed on 25/03/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1797.