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:  101
	Description:  Crystal Structure of the Complex of Human Epidermal Growth Factor and Receptor Extracellular Domains. PDB Id:  1IVO Resolution:  3.3Å Species:  Human References:  70

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 24 ⤷ pKd 9.7 (Kd 1.9x10-10 M) [24] afatinib Hs Inhibition 9.6 pKd 24 ⤷ pKd 9.6 (Kd 2.5x10-10 M) [24] erlotinib Hs Inhibition 9.2 pKd 24 ⤷ pKd 9.2 (Kd 6.7x10-10 M) [24] gefitinib 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 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 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 Hs Inhibition 7.3 pKd 110 ⤷ pKd 7.3 (Kd 4.6x10-8 M) [110] xiliertinib Hs Inhibition 10.3 pKi 79 ⤷ pKi 10.3 (Ki 5x10-11 M) [79] gefitinib Hs Inhibition 8.3 pKi 98 ⤷ pKi 8.3 (Ki 5.5x10-9 M) [98] PD166285 Hs Inhibition 7.1 pKi 71 ⤷ pKi 7.1 (Ki 8.75x10-8 M) [71] rociletinib Hs Inhibition 6.5 pKi 94 ⤷ pKi 6.5 (Ki 3.033x10-7 M) [94] AG 9 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] Hs Inhibition 11.2 pIC50 11 ⤷ pIC50 11.2 (IC50 6x10-12 M) [11] BPIQ-I Hs Inhibition 10.6 pIC50 81 ⤷ pIC50 10.6 (IC50 2.5x10-11 M) [81] TQB3804 Hs Inhibition 9.7 – 9.8 pIC50 102 ⤷ pIC50 9.8 (IC50 1.6x10-10 M) [102] Description: Inhibition of EGFR L858R/T790M/C797S triple mutant pIC50 9.7 (IC50 2.2x10-10 M) [102] Description: Inhibition of EGFR Del19/T790M/C797S triple mutant JBJ-04-125-02 Hs Inhibition 9.6 pIC50 89 ⤷ pIC50 9.6 (IC50 2.6x10-10 M) [89] Description: Inhibition of EGFRL858R/T790M in a biochemical assay CH7233163 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 Hs Inhibition 9.5 pIC50 52 ⤷ pIC50 9.5 (IC50 3x10-10 M) [52] tesevatinib Hs Inhibition 9.5 pIC50 35 ⤷ pIC50 9.5 (IC50 3x10-10 M) [35] mifanertinib Hs Inhibition 9.4 pIC50 105 ⤷ pIC50 9.4 (IC50 4x10-10 M) [105] PD 174265 Hs Inhibition 9.4 pIC50 30 ⤷ pIC50 9.4 (IC50 4.5x10-10 M) [30] allitinib Hs Inhibition 9.3 pIC50 103 ⤷ pIC50 9.3 (IC50 5x10-10 M) [103] BI-4020 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 Hs Inhibition 9.0 pIC50 109 ⤷ pIC50 9.0 (IC50 1x10-9 M) [109] nazartinib Hs Inhibition >9.0 pIC50 64 ⤷ pIC50 >9.0 (IC50 <1x10-9 M) [64] Description: Biochemical assay using EGFR L858R/T790M with a 90 minute preincubation with the inhibitor. pirotinib Hs Inhibition 9.0 pIC50 43 ⤷ pIC50 9.0 (IC50 1x10-9 M) [43] zorifertinib Hs Inhibition 8.1 – 9.5 pIC50 107 ⤷ pIC50 9.5 (IC50 3x10-10 M) [107] Description: Inhibition of wild type EGFR in vitro, at Km of ATP. pIC50 8.1 (IC50 7.2x10-9 M) [107] Description: Inhibition of EGFRL858R in vitro. canertinib Hs Inhibition 8.8 pIC50 84 ⤷ pIC50 8.8 (IC50 1.5x10-9 M) [84] Description: Inhibition of kinase activity almonertinib Hs Inhibition 8.7 pIC50 106 ⤷ pIC50 8.7 (IC50 1.89x10-9 M) [106] Description: Inhibition of wild type EGFR enzyme activity in a TR-FRET assay AEE788 Hs Inhibition 8.7 pIC50 90 ⤷ pIC50 8.7 (IC50 2x10-9 M) [90] afatinib 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 Hs Inhibition 8.6 pIC50 13 ⤷ pIC50 8.6 (IC50 2.4x10-9 M) [13] 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 98-99 ⤷ pIC50 7.8 – 9.2 (IC50 1.45x10-8 – 6x10-10 M) [98-99] falnidamol Hs Inhibition 8.5 pIC50 85 ⤷ pIC50 8.5 (IC50 3x10-9 M) [85] PKI166 Hs Inhibition 8.4 pIC50 49 ⤷ pIC50 8.4 (IC50 3.7x10-9 M) [49] JAK3 inhibitor II Hs Inhibition 8.4 pIC50 18 ⤷ pIC50 8.4 (IC50 4x10-9 M) [18] sapitinib Hs Inhibition 8.4 pIC50 9 ⤷ pIC50 8.4 (IC50 4x10-9 M) [9] zipalertinib 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 Hs Inhibition 8.3 pIC50 65 ⤷ pIC50 8.3 (IC50 5x10-9 M) [65] ibrutinib Hs Inhibition 8.3 pIC50 12 ⤷ pIC50 8.3 (IC50 5.3x10-9 M) [12] JND3229 Hs Inhibition 8.2 pIC50 62 ⤷ pIC50 8.2 (IC50 5.8x10-9 M) [62] Description: Inhibition of EGFRdel19/T790M/C797S AG1478 Hs Inhibition 8.2 pIC50 91 ⤷ pIC50 8.2 (IC50 6x10-9 M) [91] dacomitinib Hs Inhibition 8.2 pIC50 8 ⤷ pIC50 8.2 (IC50 6x10-9 M) [8] compound 38 [PMID: 24915291] Hs Inhibition 8.1 pIC50 58 ⤷ pIC50 8.1 (IC50 7x10-9 M) [58] abivertinib Hs Inhibition 8.1 pIC50 104 ⤷ pIC50 8.1 (IC50 7.68x10-9 M) [104] Description: In a biochemical assay. poziotinib Hs Inhibition 8.1 pIC50 68 ⤷ pIC50 8.1 (IC50 8x10-9 M) [68] example 10 [CN110740999A] 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 Hs Inhibition 8.0 pIC50 83 ⤷ pIC50 8.0 (IC50 1.02x10-8 M) [83] ZM-306416 Hs Inhibition 8.0 pIC50 4 ⤷ pIC50 8.0 (IC50 1x10-8 M) [4] pyrotinib Hs Irreversible inhibition 7.9 pIC50 57 ⤷ pIC50 7.9 (IC50 1.3x10-8 M) [57] selatinib Hs Inhibition 7.9 pIC50 108 ⤷ pIC50 7.9 (IC50 1.3x10-8 M) [108] dosimertinib Hs Inhibition 6.9 – 8.8 pIC50 67 ⤷ pIC50 8.8 (IC50 1.7x10-9 M) [67] Description: Enzymatic inhibitory activity vs. L858R/T790M EGFR pIC50 6.9 (IC50 1.138x10-7 M) [67] Description: Enzymatic inhibitory activity vs. WT EGFR PD 158780 Hs Inhibition 7.8 pIC50 80 ⤷ pIC50 7.8 (IC50 1.5x10-8 M) [80] Description: Inhibition of EGFR autophosphorylation BLU945 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] 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] 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 Hs Inhibition 7.7 pIC50 22 ⤷ pIC50 7.7 (IC50 2x10-8 M) [22] lazertinib Hs Inhibition >7.7 pIC50 86 ⤷ pIC50 >7.7 (IC50 <2x10-8 M) [86] 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 27 ⤷ pIC50 7.7 (IC50 2.1x10-8 M) [27] C34 [Zhu et al., 2023] Hs Inhibition 7.0 – 8.3 pIC50 111 ⤷ pIC50 8.3 (IC50 5.1x10-9 M) [111] Description: Inhibition of EGFR triple mutant L858R/T790M/C797S pIC50 7.0 (IC50 1.06x10-7 M) [111] Description: Inhibition of wild type hEGFR lifirafenib Hs Inhibition 7.5 pIC50 87 ⤷ pIC50 7.5 (IC50 2.9x10-8 M) [87] Description: Inhibition of wild type EGFR kinase domain (aa669-1210) compound 6g [PMID: 30633509] Hs Inhibition 7.5 pIC50 82 ⤷ pIC50 7.5 (IC50 3x10-8 M) [82] BMS-599626 Hs Inhibition 7.5 pIC50 32 ⤷ pIC50 7.5 (IC50 3.2x10-8 M) [32] AZ5104 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 icotinib 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 Hs Inhibition 7.3 pIC50 60 ⤷ pIC50 7.3 (IC50 4.8x10-8 M) [60] Description: Enzymatic activity inhibition of EGFRL858R/T790M sunvozertinib 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 Hs Inhibition 7.0 pIC50 78 ⤷ pIC50 7.0 (IC50 9.2x10-8 M) [78] Description: Inhibition of autophosphorylation of the cytoplasmic domain of the RTK in a cell free system. mobocertinib 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 Hs Inhibition 6.9 pIC50 34 ⤷ pIC50 6.9 (IC50 1.25x10-7 M) [34] Description: Measuring inhibition of substrate phosphorylation. brigatinib Hs Inhibition 6.9 pIC50 50 ⤷ pIC50 6.9 (IC50 1.29x10-7 M) [50] 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 37 ⤷ pIC50 6.6 (IC50 2.5x10-7 M) [37] ralimetinib 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 Hs Inhibition 6.6 pIC50 5 ⤷ pIC50 6.6 (IC50 2.6x10-7 M) [5] BI-4142 Hs Inhibition 6.6 pIC50 97 ⤷ pIC50 6.6 (IC50 2.7x10-7 M) [97] Description: Inhibition of autophosphorylation of WT EGFR overexpressed in HEK293 cells vandetanib Hs Inhibition 6.5 pIC50 16 ⤷ pIC50 6.5 (IC50 3x10-7 M) [16] mavelertinib Hs Inhibition 6.5 pIC50 76 ⤷ pIC50 6.5 (IC50 3.07x10-7 M) [76] olmutinib Hs Inhibition 6.0 – 7.0 pIC50 17 ⤷ pIC50 6.0 – 7.0 (IC50 1x10-6 – 1x10-7 M) [17] Description: Biochemical assay tuxobertinib 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 Hs Inhibition 6.4 pIC50 33 ⤷ pIC50 6.4 (IC50 4x10-7 M) [33] Description: Inhibition of substrate phosphorylation. tucatinib 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 Hs Inhibition 6.3 pIC50 95 ⤷ pIC50 6.3 (IC50 4.94x10-7 M) [95] compound 19a [PMID: 30503936] Hs Inhibition 6.3 pIC50 77 ⤷ pIC50 6.3 (IC50 5.2x10-7 M) [77] zongertinib Hs Inhibition 6.2 pIC50 96 ⤷ pIC50 6.2 (IC50 5.79x10-7 M) [96] Description: Inhibition of wild type EGFR phosphorylation acalabrutinib Hs Inhibition <6.0 pIC50 12 ⤷ pIC50 <6.0 (IC50 >1x10-6 M) [12] dovitinib Hs Inhibition 5.7 pIC50 92 ⤷ pIC50 5.7 (IC50 2x10-6 M) [92] orantinib Hs Inhibition <4.0 pIC50 47 ⤷ pIC50 <4.0 (IC50 >1x10-4 M) [47] naquotinib Hs Inhibition - - 66 ⤷ [66] tarloxotinib Hs Inhibition - - 75 ⤷ [75] firmonertinib Hs Inhibition - - 63 ⤷ [63] rezivertinib Hs Inhibition - - 74 ⤷ [74] befotertinib 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 [94]. Olmutinib potently inhibits EGFR in in vitro biochemical assay, but this does not translate to inhibition in vitro cellular assays [72].

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 88 ⤷ pIC50 10.1 (IC50 8.3x10-11 M) [88] Description: Inhibition of enzyme activity of triple mutant EGFR L858R/T790M/C797S EGFR inhibitor 57 Hs Inhibition 7.7 – 8.7 pIC50 69 ⤷ pIC50 8.7 (IC50 2x10-9 M) [69] Description: Inhibition potency for EGFR with the L858R/T790M/C797S triple mutation. pIC50 7.7 (IC50 2x10-8 M) [69] Description: Inhibition potency for EGFR with the L858R/C797S double mutation EAI045 Hs Inhibition - - 45 ⤷ [45]

Antibodies
Key to terms and symbols		Click column headers to sort
Antibody Sp. Action Value Parameter Reference panitumumab Hs Antagonist 10.3 pKd 29 ⤷ pKd 10.3 (Kd 5x10-11 M) [29] necitumumab 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 Hs Binding 9.4 pKd 36 ⤷ pKd 9.4 (Kd 3.9x10-10 M) [36] amivantamab 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 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} 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: 24,100
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