Gene and Protein Information
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

HER1 | avian erythroblastic leukemia viral (v-erbB) oncogene homolog | Wa5 | ERBB1

Database Links
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
	Description:  EGFR kinase domain complexed with a quinazoline inhibitor- GW572016 PDB Id:  1XKK Ligand:  lapatinib Resolution:  2.4Å Species:  Human References:  93
	Description:  Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains. PDB Id:  1IVO Resolution:  3.3Å Species:  Human References:  63

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 22 ⤷ pKd 9.7 (Kd 1.9x10-10 M) [22] afatinib Hs Inhibition 9.6 pKd 22 ⤷ pKd 9.6 (Kd 2.5x10-10 M) [22] erlotinib Hs Inhibition 9.2 pKd 22 ⤷ pKd 9.2 (Kd 6.7x10-10 M) [22] gefitinib Hs Inhibition 9.0 – 9.0 pKd 19,22 ⤷ pKd 9.0 (Kd 1x10-9 M) [22] pKd 9.0 (Kd 1.1x10-9 M) [19] MS154 Hs Inhibition 8.7 pKd 19 ⤷ pKd 8.7 (Kd 1.8x10-9 M) [19] Description: Dissociation constant determined for wild type EGFR in a competitive binding assay. MS39 Hs Inhibition 8.0 pKd 19 ⤷ pKd 8.0 (Kd 1.1x10-8 M) [19] Description: Dissociation constant determined for wild type EGFR in a competitive binding assay. WZ4002 Hs Inhibition 7.3 pKd 101 ⤷ pKd 7.3 (Kd 4.6x10-8 M) [101] xiliertinib Hs Inhibition 10.3 pKi 72 ⤷ pKi 10.3 (Ki 5x10-11 M) [72] gefitinib Hs Inhibition 8.3 pKi 90 ⤷ pKi 8.3 (Ki 5.5x10-9 M) [90] PD166285 Hs Inhibition 7.1 pKi 64 ⤷ pKi 7.1 (Ki 8.75x10-8 M) [64] rociletinib Hs Inhibition 6.5 pKi 86 ⤷ pKi 6.5 (Ki 3.033x10-7 M) [86] AG 9 Hs Inhibition <3.4 pKi 31 ⤷ pKi <3.4 (Ki >4x10-4 M) [31] Description: Measuring phosphorylation of the EGFR exogenous substrate polyGAT [poly(Glu6Ala3Tyr)] compound 56 [PMID: 8568816] Hs Inhibition 11.2 pIC50 10 ⤷ pIC50 11.2 (IC50 6x10-12 M) [10] BPIQ-I Hs Inhibition 10.6 pIC50 74 ⤷ pIC50 10.6 (IC50 2.5x10-11 M) [74] EGFR/ErbB-2/ErbB-4 inhibitor Hs Inhibition 9.5 pIC50 47 ⤷ pIC50 9.5 (IC50 3x10-10 M) [47] tesevatinib Hs Inhibition 9.5 pIC50 32 ⤷ pIC50 9.5 (IC50 3x10-10 M) [32] mifanertinib Hs Inhibition 9.4 pIC50 96 ⤷ pIC50 9.4 (IC50 4x10-10 M) [96] PD 174265 Hs Inhibition 9.4 pIC50 27 ⤷ pIC50 9.4 (IC50 4.5x10-10 M) [27] allitinib Hs Inhibition 9.3 pIC50 94 ⤷ pIC50 9.3 (IC50 5x10-10 M) [94] erlotinib Hs Inhibition 9.0 pIC50 100 ⤷ pIC50 9.0 (IC50 1x10-9 M) [100] nazartinib Hs Inhibition >9.0 pIC50 57 ⤷ pIC50 >9.0 (IC50 <1x10-9 M) [57] Description: Biochemical assay using EGFR L858R/T790M with a 90 minute preincubation with the inhibitor. pirotinib Hs Inhibition 9.0 pIC50 40 ⤷ pIC50 9.0 (IC50 1x10-9 M) [40] zorifertinib Hs Inhibition 8.1 – 9.5 pIC50 98 ⤷ pIC50 9.5 (IC50 3x10-10 M) [98] Description: Inhibition of wild type EGFR in vitro, at Km of ATP. pIC50 8.1 (IC50 7.2x10-9 M) [98] Description: Inhibition of EGFRL858R in vitro. canertinib Hs Inhibition 8.8 pIC50 77 ⤷ pIC50 8.8 (IC50 1.5x10-9 M) [77] Description: Inhibition of kinase activity almonertinib Hs Inhibition 8.7 pIC50 97 ⤷ pIC50 8.7 (IC50 1.89x10-9 M) [97] Description: Inhibition of wild type EGFR enzyme activity in a TR-FRET assay AEE788 Hs Inhibition 8.7 pIC50 82 ⤷ pIC50 8.7 (IC50 2x10-9 M) [82] afatinib Hs Inhibition 8.0 – 9.3 pIC50 21,49 ⤷ pIC50 8.0 – 9.3 (IC50 1.1x10-8 – 5x10-10 M) [21,49] CUDC-101 Hs Inhibition 8.6 pIC50 12 ⤷ pIC50 8.6 (IC50 2.4x10-9 M) [12] compound 17b [PMID: 35286086] Hs Inhibition 8.6 pIC50 1 ⤷ pIC50 8.6 (IC50 2.5x10-9 M) [1] pelitinib Hs Inhibition 7.8 – 9.2 pIC50 90-91 ⤷ pIC50 7.8 – 9.2 (IC50 1.45x10-8 – 6x10-10 M) [90-91] falnidamol Hs Inhibition 8.5 pIC50 78 ⤷ pIC50 8.5 (IC50 3x10-9 M) [78] PKI166 Hs Inhibition 8.4 pIC50 44 ⤷ pIC50 8.4 (IC50 3.7x10-9 M) [44] JAK3 inhibitor II Hs Inhibition 8.4 pIC50 17 ⤷ pIC50 8.4 (IC50 4x10-9 M) [17] sapitinib Hs Inhibition 8.4 pIC50 9 ⤷ pIC50 8.4 (IC50 4x10-9 M) [9] zipalertinib Hs Inhibition 8.1 – 8.7 pIC50 36 ⤷ pIC50 8.7 (IC50 2x10-9 M) [36] Description: Inhibition of hEGFR with T790M/L858R mutation in a biochemical enzyme assay pIC50 8.1 (IC50 7.4x10-9 M) [36] Description: Inhibition of hEGFR with D770_N771insNPG insertion in a biochemical enzyme assay pIC50 8.1 (IC50 8x10-9 M) [36] Description: Inhibition of WT hEGFR in a biochemical enzyme assay BMS-690514 Hs Inhibition 8.3 pIC50 58 ⤷ pIC50 8.3 (IC50 5x10-9 M) [58] ibrutinib Hs Inhibition 8.3 pIC50 11 ⤷ pIC50 8.3 (IC50 5.3x10-9 M) [11] AG1478 Hs Inhibition 8.2 pIC50 83 ⤷ pIC50 8.2 (IC50 6x10-9 M) [83] dacomitinib Hs Inhibition 8.2 pIC50 8 ⤷ pIC50 8.2 (IC50 6x10-9 M) [8] compound 38 [PMID: 24915291] Hs Inhibition 8.1 pIC50 52 ⤷ pIC50 8.1 (IC50 7x10-9 M) [52] abivertinib Hs Inhibition 8.1 pIC50 95 ⤷ pIC50 8.1 (IC50 7.68x10-9 M) [95] Description: In a biochemical assay. poziotinib Hs Inhibition 8.1 pIC50 61 ⤷ pIC50 8.1 (IC50 8x10-9 M) [61] lapatinib Hs Inhibition 8.0 pIC50 76 ⤷ pIC50 8.0 (IC50 1.02x10-8 M) [76] ZM-306416 Hs Inhibition 8.0 pIC50 4 ⤷ pIC50 8.0 (IC50 1x10-8 M) [4] pyrotinib Hs Irreversible inhibition 7.9 pIC50 51 ⤷ pIC50 7.9 (IC50 1.3x10-8 M) [51] selatinib Hs Inhibition 7.9 pIC50 99 ⤷ pIC50 7.9 (IC50 1.3x10-8 M) [99] dosimertinib Hs Inhibition 6.9 – 8.8 pIC50 60 ⤷ pIC50 8.8 (IC50 1.7x10-9 M) [60] Description: Enzymatic inhibitory activity vs. L858R/T790M EGFR pIC50 6.9 (IC50 1.138x10-7 M) [60] Description: Enzymatic inhibitory activity vs. WT EGFR PD 158780 Hs Inhibition 7.8 pIC50 73 ⤷ pIC50 7.8 (IC50 1.5x10-8 M) [73] Description: Inhibition of EGFR autophosphorylation BLU945 Hs Inhibition >7.8 pIC50 13 ⤷ pIC50 >7.8 (IC50 <1.5x10-8 M) [13] 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 52 [PMID: 36749735] Hs Inhibition 7.6 – 7.8 pIC50 50 ⤷ pIC50 7.8 (IC50 1.5x10-8 M) [50] Description: Inhibition of EGFRL858R/T790M enzyme activity pIC50 7.6 (IC50 2.5x10-8 M) [50] Description: Inhibition of WT EGFR enzymatic activity EGFR/ErbB-2 inhibitor Hs Inhibition 7.7 pIC50 20 ⤷ pIC50 7.7 (IC50 2x10-8 M) [20] lazertinib Hs Inhibition >7.7 pIC50 79 ⤷ pIC50 >7.7 (IC50 <2x10-8 M) [79] 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 24 ⤷ pIC50 7.7 (IC50 2.1x10-8 M) [24] lifirafenib Hs Inhibition 7.5 pIC50 80 ⤷ pIC50 7.5 (IC50 2.9x10-8 M) [80] Description: Inhibition of wild type EGFR kinase domain (aa669-1210) compound 6g [PMID: 30633509] Hs Inhibition 7.5 pIC50 75 ⤷ pIC50 7.5 (IC50 3x10-8 M) [75] BMS-599626 Hs Inhibition 7.5 pIC50 29 ⤷ pIC50 7.5 (IC50 3.2x10-8 M) [29] AZ5104 Hs Inhibition 7.5 pIC50 18 ⤷ pIC50 7.5 (IC50 3.3x10-8 M) [18] Description: Inhibition of wild type EGFR phosphorylation in human LoVo cells icotinib Hs Inhibition 7.3 pIC50 38 ⤷ pIC50 7.3 (IC50 4.5x10-8 M) [38] Description: Inhibition of EGFR-mediated intracellular tyrosine phosphorylation in EGF-stimulated human A431 cells. DBPR112 Hs Inhibition 7.3 pIC50 54 ⤷ pIC50 7.3 (IC50 4.8x10-8 M) [54] Description: Enzymatic activity inhibition of EGFRL858R/T790M sunvozertinib Hs Inhibition 7.1 pIC50 53 ⤷ pIC50 7.1 (IC50 8.04x10-8 M) [53] Description: Inhibition of WT EGFR phosphorylation in A431 cells neratinib Hs Inhibition 7.0 pIC50 71 ⤷ pIC50 7.0 (IC50 9.2x10-8 M) [71] Description: Inhibition of autophosphorylation of the cytoplasmic domain of the RTK in a cell free system. mobocertinib Hs Inhibition 7.0 pIC50 39 ⤷ pIC50 7.0 (IC50 1x10-7 M) [39] Description: Inhibition of EGFR harbouring concurring exon 21, L858R and T790M mutations. AG 112 Hs Inhibition 6.9 pIC50 31 ⤷ pIC50 6.9 (IC50 1.25x10-7 M) [31] Description: Measuring inhibition of substrate phosphorylation. brigatinib Hs Inhibition 6.9 pIC50 45 ⤷ pIC50 6.9 (IC50 1.29x10-7 M) [45] PF-670462 Hs Inhibition 6.8 pIC50 7 ⤷ pIC50 6.8 (IC50 1.5x10-7 M) [7] Description: In a biochemical kinase assay. PP1 Hs Inhibition 6.6 pIC50 34 ⤷ pIC50 6.6 (IC50 2.5x10-7 M) [34] PP121 Hs Inhibition 6.6 pIC50 5 ⤷ pIC50 6.6 (IC50 2.6x10-7 M) [5] BI-4142 Hs Inhibition 6.6 pIC50 89 ⤷ pIC50 6.6 (IC50 2.7x10-7 M) [89] Description: Inhibition of autophosphorylation of WT EGFR overexpressed in HEK293 cells vandetanib Hs Inhibition 6.5 pIC50 15 ⤷ pIC50 6.5 (IC50 3x10-7 M) [15] mavelertinib Hs Inhibition 6.5 pIC50 69 ⤷ pIC50 6.5 (IC50 3.07x10-7 M) [69] olmutinib Hs Inhibition 6.0 – 7.0 pIC50 16 ⤷ pIC50 6.0 – 7.0 (IC50 1x10-6 – 1x10-7 M) [16] Description: Biochemical assay tuxobertinib Hs Inhibition 6.3 – 6.5 pIC50 25 ⤷ pIC50 6.3 – 6.5 (IC50 5x10-7 – 3x10-7 M) [25] Description: Inhibition of WT EGFR kinase activity AG 490 Hs Inhibition 6.4 pIC50 30 ⤷ pIC50 6.4 (IC50 4x10-7 M) [30] Description: Inhibition of substrate phosphorylation. tucatinib Hs Inhibition 6.3 pIC50 48 ⤷ pIC50 6.3 (IC50 4.49x10-7 M) [48] Description: Inhibition of enzyme activity in a biochemical assay. osimertinib Hs Inhibition 6.3 pIC50 87 ⤷ pIC50 6.3 (IC50 4.94x10-7 M) [87] compound 19a [PMID: 30503936] Hs Inhibition 6.3 pIC50 70 ⤷ pIC50 6.3 (IC50 5.2x10-7 M) [70] zongertinib Hs Inhibition 6.2 pIC50 88 ⤷ pIC50 6.2 (IC50 5.79x10-7 M) [88] Description: Inhibition of wild type EGFR phosphorylation acalabrutinib Hs Inhibition <6.0 pIC50 11 ⤷ pIC50 <6.0 (IC50 >1x10-6 M) [11] dovitinib Hs Inhibition 5.7 pIC50 84 ⤷ pIC50 5.7 (IC50 2x10-6 M) [84] orantinib Hs Inhibition <4.0 pIC50 43 ⤷ pIC50 <4.0 (IC50 >1x10-4 M) [43] naquotinib Hs Inhibition - - 59 ⤷ [59] tarloxotinib Hs Inhibition - - 68 ⤷ [68] furmonertinib Hs Inhibition - - 56 ⤷ [56] rezivertinib Hs Inhibition - - 67 ⤷ [67]
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 [86]. Olmutinib potently inhibits EGFR in in vitro biochemical assay, but this does not translate to inhibition in vitro cellular assays [65].

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 Hs Negative 10.1 pIC50 81 ⤷ pIC50 10.1 (IC50 8.3x10-11 M) [81] Description: Inhibition of enzyme activity of triple mutant EGFR L858R/T790M/C797S EGFR inhibitor 57 Hs Inhibition 7.7 – 8.7 pIC50 62 ⤷ pIC50 8.7 (IC50 2x10-9 M) [62] Description: Inhibition potency for EGFR with the L858R/T790M/C797S triple mutation. pIC50 7.7 (IC50 2x10-8 M) [62] Description: Inhibition potency for EGFR with the L858R/C797S double mutation EAI045 Hs Inhibition - - 42 ⤷ [42]

Antibodies
Key to terms and symbols		Click column headers to sort
Antibody Sp. Action Value Parameter Reference panitumumab Hs Antagonist 10.3 pKd 26 ⤷ pKd 10.3 (Kd 5x10-11 M) [26] necitumumab Hs Binding 9.5 pKd 55 ⤷ pKd 9.5 (Kd 3.2x10-10 M) [55] Description: Binding affinity of whole IMC-11F8 IgG using BIAcore sensor technology. cetuximab Hs Binding 9.4 pKd 33 ⤷ pKd 9.4 (Kd 3.9x10-10 M) [33] amivantamab Hs Binding 8.9 pKd 41 ⤷ pKd 8.9 (Kd 1.4x10-9 M) [41] Description: Binding affinity determined by surface plasmon resonance. MM-151 Hs Binding - - 35,46 ⤷ [35,46]

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: 22,92
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