General Information of Drug Therapeutic Target (DTT) (ID: TTDC8N2)

DTT Name Erbb3 tyrosine kinase receptor (Erbb-3)
Synonyms Tyrosine kinase-type cell surface receptor HER3; Receptor tyrosine-protein kinase erbB-3; Proto-oncogene-like protein c-ErbB-3; HER3; C-erbB3; C-erbB-3 protein
Gene Name ERBB3
DTT Type
Clinical trial target
[1]
BioChemical Class
Kinase
UniProt ID
ERBB3_HUMAN
TTD ID
T86350
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.10.1
Sequence
MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVM
GNLEIVLTGHNADLSFLQWIREVTGYVLVAMNEFSTLPLPNLRVVRGTQVYDGKFAIFVM
LNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNG
RSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQD
TDCFACRHFNDSGACVPRCPQPLVYNKLTFQLEPNPHTKYQYGGVCVASCPHNFVVDQTS
CVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGN
LDFLITGLNGDPWHKIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGG
RSLYNRGFSLLIMKNLNVTSLGFRSLKEISAGRIYISANRQLCYHHSLNWTKVLRGPTEE
RLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEP
REFAHEAECFSCHPECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPI
YKYPDVQNECRPCHENCTQGCKGPELQDCLGQTLVLIGKTHLTMALTVIAGLVVIFMMLG
GTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVF
GTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPG
SSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNV
LLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVT
VWELMTFGAEPYAGLRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDENIRPTFKE
LANEFTRMARDPPRYLVIKRESGPGIAPGPEPHGLTNKKLEEVELEPELDLDLDLEAEED
NLATTTLGSALSLPVGTLNRPRGSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPR
PVSLHPMPRGCLASESSEGHVTGSEAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLL
TPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLSSVLGTEEEDEDEEYEYM
NRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDY
EYMNRQRDGGGPGGDYAAMGACPASEQGYEEMRAFQGPGHQAPHVHYARLKTLRSLEATD
SAFDNPDYWHSRLFPKANAQRT
Function
Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase. May also be activated by CSPG5. Involved in the regulation of myeloid cell differentiation. Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.
KEGG Pathway
ErbB signaling pathway (hsa04012 )
Calcium signaling pathway (hsa04020 )
Endocytosis (hsa04144 )
Proteoglycans in cancer (hsa05205 )
MicroRNAs in cancer (hsa05206 )
Reactome Pathway
Signaling by ERBB4 (R-HSA-1236394 )
SHC1 events in ERBB2 signaling (R-HSA-1250196 )
PIP3 activates AKT signaling (R-HSA-1257604 )
GRB7 events in ERBB2 signaling (R-HSA-1306955 )
Downregulation of ERBB2 (R-HSA-1358803 )
PI3K events in ERBB2 signaling (R-HSA-1963642 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
RAF/MAP kinase cascade (R-HSA-5673001 )
ERBB2 Regulates Cell Motility (R-HSA-6785631 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
ERBB2 Activates PTK6 Signaling (R-HSA-8847993 )
Downregulation of ERBB2 signaling (R-HSA-8863795 )
Signaling by ERBB2 KD Mutants (R-HSA-9664565 )
Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686 )
Signaling by ERBB2 (R-HSA-1227986 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
22 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CDX-3379 DM5GKYD Squamous cell carcinoma 2B60-2D01 Phase 2 [2]
Elisidepsin DMB38KH Psoriasis vulgaris EA90 Phase 2 [1]
MEHD-7945A DMHOF7T Colorectal cancer 2B91.Z Phase 2 [3]
MM-121 DMDJRU1 Breast cancer 2C60-2C65 Phase 2 [4]
MM-141 DM2RJ4D Pancreatic cancer 2C10 Phase 2 [5]
Seribantumab DMYT470 Colorectal cancer 2B91.Z Phase 2 [2]
Zenocutuzumab DM1FLHH Pancreatic cancer 2C10 Phase 2 [6]
AMG888/U3-1287 DMEF4L5 Non-small-cell lung cancer 2C25.Y Phase 1/2 [7]
LJM716 DMGTB5N Breast cancer 2C60-2C65 Phase 1/2 [8]
Sym013 DMZM6I2 Epithelial ovarian cancer 2B5D Phase 1/2 [9]
Zenocutuzomab DMMQGPE Solid tumour/cancer 2A00-2F9Z Phase 1/2 [10]
Anti-HER3/EGFR DAF DMDMNJ6 Metastatic epithelial tumour 2D60 Phase 1 [3]
AV-203 DMZLCTD Solid tumour/cancer 2A00-2F9Z Phase 1 [11]
Drug 2849330 DMM57CS Solid tumour/cancer 2A00-2F9Z Phase 1 [12]
GSK2849330 DM6KE4G Solid tumour/cancer 2A00-2F9Z Phase 1 [7]
KTN3379 DM8FQPX Solid tumour/cancer 2A00-2F9Z Phase 1 [13]
MM-151 DMXQHZC Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
Patritumab DMFSMCB Non-small-cell lung cancer 2C25.Y Phase 1 [14]
Recombinant human Erbb3 fragment therapeutic tumor vaccine DMK9Y71 Solid tumour/cancer 2A00-2F9Z Phase 1 [15]
REGN1400 DME3VU8 Solid tumour/cancer 2A00-2F9Z Phase 1 [16]
RG7116 DM6XVCO Solid tumour/cancer 2A00-2F9Z Phase 1 [17]
SI-B001 DMDSFEB Metastatic epithelial tumour 2D60 Phase 1 [18]
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⏷ Show the Full List of 22 Clinical Trial Drug(s)
3 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
MP-RM-1 DMFKG7C Solid tumour/cancer 2A00-2F9Z Investigative [7]
Soluble ErbB3 theragnostics DMJXN1G Solid tumour/cancer 2A00-2F9Z Investigative [7]
SYM-011 DMKIDRY Solid tumour/cancer 2A00-2F9Z Investigative [7]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Lung cancer 2C82 Lung tissue 7.21E-05 -0.32 -0.62
Breast cancer 2C82 Breast tissue 3.51E-01 0.1 0.17
Psoriasis EA90 Skin 6.18E-05 -0.33 -0.75
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References

1 Molecular pharmacodynamics of PM02734 (elisidepsin) as single agent and in combination with erlotinib; synergistic activity in human non-small cell lung cancer cell lines and xenograft models. Eur J Cancer. 2009 Jul;45(10):1855-64.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Company report (Biooncology)
4 Company report (Merrimack)
5 MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol Cancer Ther. 2014 Feb;13(2):410-25.
6 Zenocutuzumab, a HER2xHER3 Bispecific Antibody, Is Effective Therapy for Tumors Driven by NRG1 Gene Rearrangements. Cancer Discov. 2022 May 2;12(5):1233-1247.
7 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1798).
8 An antibody that locks HER3 in the inactive conformation inhibits tumor growth driven by HER2 or neuregulin. Cancer Res. 2013 Oct 1;73(19):6024-35.
9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
10 Clinical pipeline report, company report or official report of Merus.
11 Neuregulin 1 expression is a predictive biomarker for response to AV-203, an ERBB3 inhibitory antibody, in human tumor models. Clin Cancer Res. 2015 Mar 1;21(5):1106-14.
12 National Cancer Institute Drug Dictionary (drug id 754219).
13 A critical role for HER3 in HER2-amplified and non-amplified breast cancers: function of a kinase-dead RTK. Am J Transl Res. 2015; 7(4): 733-750.
14 Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):511-6.
15 Clinical pipeline report, company report or official report of Zensun.
16 J Clin Oncol 32:5s, 2014 (suppl; abstr 2516).
17 RG7116, a therapeutic antibody that binds the inactive HER3 receptor and is optimized for immune effector activation. Cancer Res. 2013 Aug 15;73(16):5183-94.
18 Clinical pipeline report, company report or official report of SystImmune.