Target General Infomation
Target ID
T86350 (Former ID: TTDR01265)
Target 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
Target Type
Clinical trial target
[1]
Disease [+] 10 Target-related Diseases +
1 Colorectal cancer [ICD-11: 2B91]
2 Head and neck cancer [ICD-11: 2D42]
3 Lung cancer [ICD-11: 2C25]
4 Pancreatic cancer [ICD-11: 2C10]
5 Psoriasis [ICD-11: EA90]
6 Squamous cell carcinoma [ICD-11: 2B60-2D01]
7 Breast cancer [ICD-11: 2C60-2C6Y]
8 Malignant mesenchymal neoplasm [ICD-11: 2B5D-2B5Y]
9 Metastatic lymph node neoplasm [ICD-11: 2D60]
10 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
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.
BioChemical Class
Kinase
UniProt ID
ERBB3_HUMAN
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
Drugs and Modes of Action
Clinical Trial Drug(s) [+] 19 Clinical Trial Drugs +
1 CDX-3379 Drug Info Phase 2 Squamous cell carcinoma [2]
2 Elisidepsin Drug Info Phase 2 Psoriasis vulgaris [3]
3 MEHD-7945A Drug Info Phase 2 Colorectal cancer [4], [5]
4 MM-121 Drug Info Phase 2 Breast cancer [6]
5 MM-141 Drug Info Phase 2 Solid tumour/cancer [7]
6 Seribantumab Drug Info Phase 2 Colorectal cancer [8]
7 AMG888/U3-1287 Drug Info Phase 1/2 Non-small-cell lung cancer [9]
8 LJM716 Drug Info Phase 1/2 Breast cancer [10]
9 Sym013 Drug Info Phase 1/2 Epithelial ovarian cancer [2]
10 Anti-HER3/EGFR DAF Drug Info Phase 1 Metastatic epithelial tumour [11]
11 AV-203 Drug Info Phase 1 Solid tumour/cancer [12]
12 Drug 2849330 Drug Info Phase 1 Solid tumour/cancer [13]
13 GSK2849330 Drug Info Phase 1 Solid tumour/cancer [13]
14 KTN3379 Drug Info Phase 1 Solid tumour/cancer [14]
15 MM-151 Drug Info Phase 1 Solid tumour/cancer [15]
16 Patritumab Drug Info Phase 1 Non-small-cell lung cancer [16]
17 Recombinant human Erbb3 fragment therapeutic tumor vaccine Drug Info Phase 1 Solid tumour/cancer [17]
18 REGN1400 Drug Info Phase 1 Solid tumour/cancer [18]
19 RG7116 Drug Info Phase 1 Solid tumour/cancer [19]
Mode of Action [+] 3 Modes of Action +
Inhibitor [+] 3 Inhibitor drugs +
1 Elisidepsin Drug Info [1]
2 Sym013 Drug Info [2]
3 Soluble ErbB3 theragnostics Drug Info [24]
Modulator [+] 8 Modulator drugs +
1 MEHD-7945A Drug Info [20], [21]
2 MM-121 Drug Info [22]
3 MM-141 Drug Info [23]
4 AMG888/U3-1287 Drug Info [24]
5 Anti-HER3/EGFR DAF Drug Info [20]
6 MM-151 Drug Info [23]
7 RG7116 Drug Info [33]
8 SYM-011 Drug Info [24]
Antagonist [+] 2 Antagonist drugs +
1 Seribantumab Drug Info [8]
2 CDX-3379 Drug Info [8]
Target Regulators
Target-regulating microRNAs
Target-interacting Proteins
Target Profiles in Patients
Target Expression
 Profile (TEP)
Target Affiliated Biological Pathways
KEGG Pathway [+] 5 KEGG Pathways +
1 ErbB signaling pathway
2 Calcium signaling pathway
3 Endocytosis
4 Proteoglycans in cancer
5 MicroRNAs in cancer
NetPath Pathway [+] 1 NetPath Pathways +
1 TNFalpha Signaling Pathway
Panther Pathway [+] 2 Panther Pathways +
1 Cadherin signaling pathway
2 EGF receptor signaling pathway
PID Pathway [+] 3 PID Pathways +
1 ErbB2/ErbB3 signaling events
2 ErbB receptor signaling network
3 a6b1 and a6b4 Integrin signaling
WikiPathways [+] 5 WikiPathways +
1 ErbB Signaling Pathway
2 Apoptosis-related network due to altered Notch3 in ovarian cancer
3 Signaling Pathways in Glioblastoma
4 miR-targeted genes in muscle cell - TarBase
5 Heart Development
References
REF 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.
REF 2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 3 First-in-human, phase I study of elisidepsin (PM02734) administered as a 30-min or as a 3-hour intravenous infusion every three weeks in patients with advanced solid tumors. Invest New Drugs. 2015 Aug;33(4):901-10.
REF 4 ClinicalTrials.gov (NCT01577173) A Study of MEHD7945A Versus Cetuximab in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of The Head And Neck
REF 5 ClinicalTrials.gov (NCT01652482) A Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI in Second Line in Patients With KRAS Wild-Type Metastatic Colorectal Cancer. U.S. National Institutes of Health.
REF 6 ClinicalTrials.gov (NCT01447706) A Study of MM-121 With Paclitaxel in Platinum Resistant/ Refractory Advanced Ovarian Cancers. U.S. National Institutes of Health.
REF 7 ClinicalTrials.gov (NCT02399137) A Phase 2 Study of MM-141 Plus Nab-paclitaxel and Gemcitabine in Front-line Metastatic Pancreatic Cancer. U.S. National Institutes of Health.
REF 8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 9 ClinicalTrials.gov (NCT01211483) Study of Erlotinib With or Without Investigational Drug (U3-1287) in Subjects With Advanced Non-small Cell Lung Cancer. U.S. National Institutes of Health.
REF 10 ClinicalTrials.gov (NCT02143622) Study of Efficacy and Safety of LJM716 and Cetuximab in Head and Neck Squamous Cell Carcinoma Patients. U.S. National Institutes of Health.
REF 11 Clinical pipeline report, company report or official report of Genentech (2011).
REF 12 ClinicalTrials.gov (NCT01603979) A Phase 1 Dose Escalation Study of AV-203, an ERBB3 Inhibitory Antibody, in Subjects With Advanced Solid Tumors. U.S. National Institutes of Health.
REF 13 ClinicalTrials.gov (NCT01966445) Dose Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2849330 in Subjects With Advanced Her3-Positive Solid Tumors. U.S. National Institutes of Health.
REF 14 ClinicalTrials.gov (NCT02014909) A Phase 1 Study to Evaluate the Safety and Pharmacokinetics of KTN3379 in Adult Subjects With Advanced Tumors. U.S. National Institutes of Health.
REF 15 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035447)
REF 16 ClinicalTrials.gov (NCT01957280) Study to Assess Pharmacokinetics, Immunogenicity and Safety/Tolerability of Patritumab (U3-1287). U.S. National Institutes of Health.
REF 17 Clinical pipeline report, company report or official report of Zensun.
REF 18 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800036915)
REF 19 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035594)
REF 20 Company report (Biooncology)
REF 21 Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
REF 22 Company report (Merrimack)
REF 23 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.
REF 24 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).
REF 25 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.
REF 26 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.
REF 27 National Cancer Institute Drug Dictionary (drug id 754219).
REF 28 Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
REF 29 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.
REF 30 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.
REF 31 Clinical pipeline report, company report or official report of Zensun.
REF 32 J Clin Oncol 32:5s, 2014 (suppl; abstr 2516).
REF 33 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.

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