erb-b2 receptor tyrosine kinase 3 | Type I RTKs: ErbB (epidermal growth factor) receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

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erb-b2 receptor tyrosine kinase 3

Target not currently curated in GtoImmuPdb

Target id: 1798

Nomenclature: erb-b2 receptor tyrosine kinase 3

Abbreviated Name: HER3

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 1 183 12q13 ERBB3 erb-b2 receptor tyrosine kinase 3
Mouse 1 1339 10 Erbb3 erb-b2 receptor tyrosine kinase 3
Rat 1 1339 7q11 Erbb3 erb-b2 receptor tyrosine kinase 3
Previous and Unofficial Names
lethal congenital contracture syndrome 2 | Glial growth factor receptor | LCCS2 | v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the HER3 (ERBB3) Extracellular Domain
PDB Id:  1M6B
Resolution:  2.6Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the ERBB3 kinase domain in complex with AMP-PNP
PDB Id:  3LMG
Ligand:  AMP-PNP
Resolution:  2.8Å
Species:  Human
References:  9
Enzyme Reaction
EC Number: 2.7.10.1
Natural/Endogenous Ligands
neuregulin-1 {Sp: Human}
neuregulin-2 {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
sapitinib Hs Inhibition 8.4 pIC50 1
pIC50 8.4 (IC50 4x10-9 M) [1]
TX2-121-1 Hs Binding 7.3 pIC50 6
pIC50 7.3 (IC50 4.9x10-8 M) [6]
Inhibitor Comments
TX2-121-1 (PubChem CID 78243759), a compound structurally related to TX1-85-1, is similarly reported to down-regulate HER3-dependent signalling [6].
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
elgemtumab Hs Binding 10.6 – 11.4 pKd 5
pKd 10.6 – 11.4 (Kd 2.6x10-11 – 4x10-12 M) [5]
seribantumab Hs Binding 9.1 pKd 8
pKd 9.1 (Kd 7.69x10-10 M) [8]
istiratumab Hs Binding >9.0 pKd 4
pKd >9.0 (Kd <1x10-9 M) [4]
MM-111 Hs Binding 7.8 pKd 7
pKd 7.8 (Kd 1.561x10-8 M) [7]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
TX1-85-1 Hs Binding 7.6 pIC50 6
pIC50 7.6 (IC50 2.3x10-8 M) [6]
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: 3,10

Key to terms and symbols Click column headers to sort
Target used in screen: ERBB3
Ligand Sp. Type Action Value Parameter
bosutinib Hs Inhibitor Inhibition 9.1 pKd
neratinib Hs Inhibitor Inhibition 8.1 pKd
dasatinib Hs Inhibitor Inhibition 7.7 pKd
PP-242 Hs Inhibitor Inhibition 6.9 pKd
PD-173955 Hs Inhibitor Inhibition 6.8 pKd
vandetanib Hs Inhibitor Inhibition 6.8 pKd
cediranib Hs Inhibitor Inhibition 6.7 pKd
canertinib Hs Inhibitor Inhibition 6.7 pKd
gefitinib Hs Inhibitor Inhibition 6.1 pKd
erlotinib Hs Inhibitor Inhibition 6.0 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Lethal congenital contractural syndrome 2; LCCS2
OMIM: 607598
Orphanet: ORPHA137776

References

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1. Barlaam B, Anderton J, Ballard P, Bradbury RH, Hennequin LF, Hickinson DM, Kettle JG, Kirk G, Klinowska T, Lambert-van der Brempt C et al.. (2013) Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR, HER2, and HER3 Receptors. ACS Med Chem Lett, 4 (8): 742-6. [PMID:24900741]

2. Cho HS, Leahy DJ. (2002) Structure of the extracellular region of HER3 reveals an interdomain tether. Science, 297 (5585): 1330-3. [PMID:12154198]

3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

4. Fitzgerald JB, Johnson BW, Baum J, Adams S, Iadevaia S, Tang J, Rimkunas V, Xu L, Kohli N, Rennard R et al.. (2014) MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol. Cancer Ther., 13 (2): 410-25. [PMID:24282274]

5. Garner AP, Sprague EAR, Ettenberg SA, Kunz C, Haubst N, Elis W. (2014) Antibodies for epidermal growth factor receptor 3 (HER3). Patent number: US8735551 B2. Assignee: Novartis Ag.. Priority date: 20/08/2010. Publication date: 27/05/2014.

6. Lim SM, Xie T, Westover KD, Ficarro SB, Tae HS, Gurbani D, Sim T, Marto JA, Jänne PA, Crews CM et al.. (2015) Development of small molecules targeting the pseudokinase Her3. Bioorg. Med. Chem. Lett., 25 (16): 3382-9. [PMID:26094118]

7. McDonagh CF, Huhalov A, Harms BD, Adams S, Paragas V, Oyama S, Zhang B, Luus L, Overland R, Nguyen S et al.. (2012) Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3. Mol. Cancer Ther., 11 (3): 582-93. [PMID:22248472]

8. Schoeberl B, Pace EA, Fitzgerald JB, Harms BD, Xu L, Nie L, Linggi B, Kalra A, Paragas V, Bukhalid R et al.. (2009) Therapeutically targeting ErbB3: a key node in ligand-induced activation of the ErbB receptor-PI3K axis. Sci Signal, 2 (77): ra31. [PMID:19567914]

9. Shi F, Telesco SE, Liu Y, Radhakrishnan R, Lemmon MA. (2010) ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation. Proc. Natl. Acad. Sci. U.S.A., 107 (17): 7692-7. [PMID:20351256]

10. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]

How to cite this page

Type I RTKs: ErbB (epidermal growth factor) receptor family: erb-b2 receptor tyrosine kinase 3. Last modified on 11/07/2016. Accessed on 19/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1798.