erb-b2 receptor tyrosine kinase 2 | Type I RTKs: ErbB (epidermal growth factor) receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

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erb-b2 receptor tyrosine kinase 2

Target not currently curated in GtoImmuPdb

Target id: 2019

Nomenclature: erb-b2 receptor tyrosine kinase 2

Abbreviated Name: HER2

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 1225 17q11.2-q12 ERBB2 erb-b2 receptor tyrosine kinase 2
Mouse 1 1225 11 D Erbb2 erb-b2 receptor tyrosine kinase 2
Rat 1 1259 10 q32.1 Erbb2 erb-b2 receptor tyrosine kinase 2
Previous and Unofficial Names
CD340 | c-erbB2 | epidermal growth factor receptor-related protein | Neu oncogene | NEU proto-oncogene | p185neu | v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 | v-erb-b2 avian erythroblastic leukemia viral oncogene 2
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the kinase domain of human HER2 (ERBB2).
PDB Id:  3PP0
Resolution:  2.25Å
Species:  Human
References:  1
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of extracellular domain of human HER2 complexed with Herceptin Fab.
PDB Id:  1N8Z
Ligand:  trastuzumab
Resolution:  2.52Å
Species:  Human
References:  8
Enzyme Reaction
EC Number:

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

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
neratinib Hs Inhibition 8.2 pKd 10
pKd 8.2 (Kd 6x10-9 M) [10]
lapatinib Hs Inhibition 8.1 pKd 10
pKd 8.1 (Kd 7x10-9 M) [10]
EGFR/ErbB-2/ErbB-4 inhibitor Hs Inhibition 9.0 pIC50 17
pIC50 9.0 (IC50 1.1x10-9 M) [17]
allitinib Hs Inhibition 8.5 pIC50 32
pIC50 8.5 (IC50 3x10-9 M) [32]
poziotinib Hs Inhibition 8.3 pIC50 25
pIC50 8.3 (IC50 5.3x10-9 M) [25]
mubritinib Hs Inhibition 8.2 pIC50 24
pIC50 8.2 (IC50 6x10-9 M) [24]
Description: Measuring tyrosine phosphorylation of HER2 in human bladder cancer cell lineT24.
AEE788 Hs Inhibition 8.2 pIC50 30
pIC50 8.2 (IC50 6x10-9 M) [30]
ibrutinib Hs Inhibition 8.2 pIC50 5
pIC50 8.2 (IC50 6.4x10-9 M) [5]
tucatinib Hs Inhibition 8.2 pIC50 18
pIC50 8.2 (IC50 6.9x10-9 M) [18]
Description: Inhibition of enzyme activity in a biochemical assay.
compound 38 [PMID: 24915291] Hs Inhibition 8.1 pIC50 21
pIC50 8.1 (IC50 7x10-9 M) [21]
selatinib Hs Inhibition 8.1 pIC50 33
pIC50 8.1 (IC50 8.5x10-9 M) [33]
canertinib Hs Inhibition 8.1 pIC50 28
pIC50 8.1 (IC50 9x10-9 M) [28]
Description: Inhibition of ErbB2 autophosphorylation
lapatinib Hs Inhibition 8.0 pIC50 27
pIC50 8.0 (IC50 9.8x10-9 M) [27]
CP-724714 Hs Inhibition 7.9 pIC50 13
pIC50 7.9 (IC50 1.2x10-8 M) [13]
afatinib Hs Inhibition 7.8 pIC50 19
pIC50 7.8 (IC50 1.4x10-8 M) [19]
sapitinib Hs Inhibition 7.8 pIC50 4
pIC50 7.8 (IC50 1.4x10-8 M) [4]
tesevatinib Hs Inhibition 7.8 pIC50 12
pIC50 7.8 (IC50 1.6x10-8 M) [12]
CUDC-101 Hs Inhibition 7.8 pIC50 6
pIC50 7.8 (IC50 1.57x10-8 M) [6]
BMS-690514 Hs Inhibition 7.7 pIC50 22
pIC50 7.7 (IC50 1.9x10-8 M) [22]
BMS-599626 Hs Inhibition 7.5 pIC50 11
pIC50 7.5 (IC50 2.2x10-8 M) [11]
pyrotinib Hs Irreversible inhibition 7.4 pIC50 20
pIC50 7.4 (IC50 3.8x10-8 M) [20]
dacomitinib Hs Inhibition 7.3 pIC50 3
pIC50 7.3 (IC50 4.6x10-8 M) [3]
neratinib Hs Inhibition 7.2 pIC50 26
pIC50 7.2 (IC50 5.9x10-8 M) [26]
Description: Inhibition of autophosphorylation of the cytoplasmic domain of the RTK in a cell free system.
EGFR/ErbB-2 inhibitor Hs Inhibition 7.1 pIC50 9
pIC50 7.1 (IC50 7.9x10-8 M) [9]
acalabrutinib Hs Inhibition <6.0 pIC50 5
pIC50 <6.0 (IC50 >1x10-6 M) [5]
falnidamol Hs Inhibition 5.5 pIC50 29
pIC50 5.5 (IC50 3.4x10-6 M) [29]
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
MM-111 Hs Binding 9.5 pKd 23
pKd 9.5 (Kd 3x10-10 M) [23]
pertuzumab Hs Inhibition >8.0 pIC50 15
pIC50 >8.0 (IC50 <1x10-8 M) [15]
Description: Preferred value for inhibition of heregulin β1 binding to MCF7 cells.
trastuzumab Hs Inhibition - -
margetuximab Hs Binding - - 14
Antibody Comments
An anti-ERBB2/CD3e Triomab® called ertumaxomab (Rexomun®) has demonstrated antitumour efficacy against HER2/neu low-expressing breast tumours that are resistant to trastuzumab [16]. Development of ertumaxomab was not progressed beyond Phase 2 for business reasons. No safety issues had been apparent. See the entry for catumaxomab for full details of Triomab® mechanism of action.
Dragonfly Therapeutics are developing agents, using a platform called TriNKETTM (an abbreviation for tri-specific natural killer cell engagement therapies), that simultaneously engage a surface protein on target cells (e.g. cancer cells) and an as yet undisclosed natural killer (NK) cell protein so as to activate and redirect NK cells of the innate and adaptive immune system to destroy cancers. A patent held by Dragonfly Therapeutics suggests that one of the NK cell targets they are interested in is NKG2D (KLRK1; P26718) [7]. Their most advanced candidate (as of November 2019) is DF1001, a HER2-targeting TriNKETTM that has begun Phase 1/2 evaluation in HER2 +ve solid tumours (see NCT04143711). TriNKETTM therapeutics have the potential to treat autoimmune disease in addition to cancer.
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 10,31

Key to terms and symbols Click column headers to sort
Target used in screen: ERBB2
Ligand Sp. Type Action Value Parameter
afatinib Hs Inhibitor Inhibition 8.3 pKd
neratinib Hs Inhibitor Inhibition 8.2 pKd
lapatinib Hs Inhibitor Inhibition 8.1 pKd
canertinib Hs Inhibitor Inhibition 7.3 pKd
staurosporine Hs Inhibitor Inhibition 6.7 pKd
TG-100-115 Hs Inhibitor Inhibition 6.4 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.3 pKd
foretinib Hs Inhibitor Inhibition 6.2 pKd
masitinib Hs Inhibitor Inhibition 5.9 pKd
dasatinib Hs Inhibitor Inhibition 5.8 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
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.

Reference: ...2

Key to terms and symbols Click column headers to sort
Target used in screen: nd/ERBB2(HER2)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
EGFR/ErbB-2/ErbB-4 inhibitor Hs Inhibitor Inhibition 2.4
lapatinib Hs Inhibitor Inhibition 9.6
compound 56 [PMID: 8568816] Hs Inhibitor Inhibition 13.8
PDK1/Akt/Flt dual pathway inhibitor Hs Inhibitor Inhibition 22.2
AG1478 Hs Inhibitor Inhibition 22.5
PD 158780 Hs Inhibitor Inhibition 28.9
Src kinase inhibitor I Hs Inhibitor Inhibition 29.5
bosutinib Hs Inhibitor Inhibition 32.9
JAK3 inhibitor II Hs Inhibitor Inhibition 33.1
PD 174265 Hs Inhibitor Inhibition 34.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0033088 negative regulation of immature T cell proliferation in thymus IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0033088 negative regulation of immature T cell proliferation in thymus IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0033088 negative regulation of immature T cell proliferation in thymus IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0033088 negative regulation of immature T cell proliferation in thymus IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0033088 negative regulation of immature T cell proliferation in thymus IEA
Clinically-Relevant Mutations and Pathophysiology
Disease:  Gastric cancer
Synonyms: Stomach cancer
Disease Ontology: DOID:10534
OMIM: 613659
Disease:  Glioblastoma
Synonyms: Glioblastoma multiforme
Glioma susceptibility 1; GLM1 [OMIM: 137800]
Disease Ontology: DOID:3068
OMIM: 137800
Orphanet: ORPHA360
Disease:  Lung cancer
Disease Ontology: DOID:1324
OMIM: 211980
Disease:  Ovarian cancer
Disease Ontology: DOID:2394
OMIM: 167000


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8. Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW, Leahy DJ. (2003) Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature, 421 (6924): 756-60. [PMID:12610629]

9. Cockerill S, Stubberfield C, Stables J, Carter M, Guntrip S, Smith K, McKeown S, Shaw R, Topley P, Thomsen L et al.. (2001) Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2. Bioorg. Med. Chem. Lett., 11 (11): 1401-5. [PMID:11378364]

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11. Gavai AV, Fink BE, Fairfax DJ, Martin GS, Rossiter LM, Holst CL, Kim SH, Leavitt KJ, Mastalerz H, Han WC et al.. (2009) Discovery and preclinical evaluation of [4-[[1-(3-fluorophenyl)methyl]-1H-indazol-5-ylamino]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]carbamic acid, (3S)-3-morpholinylmethyl ester (BMS-599626), a selective and orally efficacious inhibitor of human epidermal growth factor receptor 1 and 2 kinases. J. Med. Chem., 52 (21): 6527-30. [PMID:19821562]

12. Gendreau SB, Ventura R, Keast P, Laird AD, Yakes FM, Zhang W, Bentzien F, Cancilla B, Lutman J, Chu F et al.. (2007) Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647. Clin. Cancer Res., 13 (12): 3713-23. [PMID:17575237]

13. Gundla R, Kazemi R, Sanam R, Muttineni R, Sarma JA, Dayam R, Neamati N. (2008) Discovery of novel small-molecule inhibitors of human epidermal growth factor receptor-2: combined ligand and target-based approach. J. Med. Chem., 51 (12): 3367-77. [PMID:18500794]

14. Johnson LS, Huang L, Tuaillon N, Bonvini E. (2014) HER2/neu-specific antibodies and methods of using same. Patent number: US8802093 B2. Assignee: Macrogenics, Inc.. Priority date: 02/04/2008. Publication date: 12/08/2014.

15. Kao Y-H, Vanderlaan M. (2006) Her2 antibody composition. Patent number: WO2006033700. Assignee: Genentech Inc.. Priority date: 22/07/2004. Publication date: 30/04/2010.

16. Kiewe P, Thiel E. (2008) Ertumaxomab: a trifunctional antibody for breast cancer treatment. Expert Opin Investig Drugs, 17 (10): 1553-8. [PMID:18808314]

17. Klutchko SR, Zhou H, Winters RT, Tran TP, Bridges AJ, Althaus IW, Amato DM, Elliott WL, Ellis PA, Meade MA et al.. (2006) Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB family of tyrosine kinase receptors. J. Med. Chem., 49 (4): 1475-85. [PMID:16480284]

18. Kulukian A, Lee P, Taylor J, Rosler R, de Vries P, Watson D, Forero-Torres A, Peterson S. (2020) Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models. Mol. Cancer Ther., 19 (4): 976-987. [PMID:32241871]

19. Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F et al.. (2008) BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene, 27 (34): 4702-11. [PMID:18408761]

20. Li X, Yang C, Wan H, Zhang G, Feng J, Zhang L, Chen X, Zhong D, Lou L, Tao W et al.. (2017) Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci, 110: 51-61. [PMID:28115222]

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22. Marathe P, Tang Y, Sleczka B, Rodrigues D, Gavai A, Wong T, Christopher L, Zhang H. (2010) Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci, 99 (8): 3579-93. [PMID:20166197]

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24. Nagasawa J, Mizokami A, Koshida K, Yoshida S, Naito K, Namiki M. (2006) Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo. Int. J. Urol., 13 (5): 587-92. [PMID:16771730]

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How to cite this page

Type I RTKs: ErbB (epidermal growth factor) receptor family: erb-b2 receptor tyrosine kinase 2. Last modified on 20/04/2020. Accessed on 02/07/2020. IUPHAR/BPS Guide to PHARMACOLOGY,