Target Information
| Target General Information | Top | |||||
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| Target ID |
T86350
(Former ID: TTDR01265)
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| Target Name |
Erbb3 tyrosine kinase receptor (Erbb-3)
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| 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
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| Gene Name |
ERBB3
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| Target Type |
Clinical trial target
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[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 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| 10 | Metastatic lymph node neoplasm [ICD-11: 2D60] | |||||
| 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.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.10.1
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| Sequence |
MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVM
GNLEIVLTGHNADLSFLQWIREVTGYVLVAMNEFSTLPLPNLRVVRGTQVYDGKFAIFVM LNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNG RSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQD TDCFACRHFNDSGACVPRCPQPLVYNKLTFQLEPNPHTKYQYGGVCVASCPHNFVVDQTS CVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGN LDFLITGLNGDPWHKIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGG RSLYNRGFSLLIMKNLNVTSLGFRSLKEISAGRIYISANRQLCYHHSLNWTKVLRGPTEE RLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEP REFAHEAECFSCHPECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPI YKYPDVQNECRPCHENCTQGCKGPELQDCLGQTLVLIGKTHLTMALTVIAGLVVIFMMLG GTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVF GTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPG SSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNV LLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVT VWELMTFGAEPYAGLRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDENIRPTFKE LANEFTRMARDPPRYLVIKRESGPGIAPGPEPHGLTNKKLEEVELEPELDLDLDLEAEED NLATTTLGSALSLPVGTLNRPRGSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPR PVSLHPMPRGCLASESSEGHVTGSEAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLL TPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLSSVLGTEEEDEDEEYEYM NRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDY EYMNRQRDGGGPGGDYAAMGACPASEQGYEEMRAFQGPGHQAPHVHYARLKTLRSLEATD SAFDNPDYWHSRLFPKANAQRT Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T14JZK | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 21 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 | Zenocutuzomab | Drug Info | Phase 1/2 | Solid tumour/cancer | [11] | |
| 11 | Anti-HER3/EGFR DAF | Drug Info | Phase 1 | Metastatic epithelial tumour | [12] | |
| 12 | AV-203 | Drug Info | Phase 1 | Solid tumour/cancer | [13] | |
| 13 | Drug 2849330 | Drug Info | Phase 1 | Solid tumour/cancer | [14] | |
| 14 | GSK2849330 | Drug Info | Phase 1 | Solid tumour/cancer | [14] | |
| 15 | KTN3379 | Drug Info | Phase 1 | Solid tumour/cancer | [15] | |
| 16 | MM-151 | Drug Info | Phase 1 | Solid tumour/cancer | [16] | |
| 17 | Patritumab | Drug Info | Phase 1 | Non-small-cell lung cancer | [17] | |
| 18 | Recombinant human Erbb3 fragment therapeutic tumor vaccine | Drug Info | Phase 1 | Solid tumour/cancer | [18] | |
| 19 | REGN1400 | Drug Info | Phase 1 | Solid tumour/cancer | [19] | |
| 20 | RG7116 | Drug Info | Phase 1 | Solid tumour/cancer | [20] | |
| 21 | SI-B001 | Drug Info | Phase 1 | Metastatic epithelial tumour | [21] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | CDX-3379 | Drug Info | [8] | |||
| 2 | Seribantumab | Drug Info | [8] | |||
| Inhibitor | [+] 4 Inhibitor drugs | + | ||||
| 1 | Elisidepsin | Drug Info | [1] | |||
| 2 | Sym013 | Drug Info | [2] | |||
| 3 | Zenocutuzomab | Drug Info | [28] | |||
| 4 | Soluble ErbB3 theragnostics | Drug Info | [26] | |||
| Modulator | [+] 8 Modulator drugs | + | ||||
| 1 | MEHD-7945A | Drug Info | [22], [23] | |||
| 2 | MM-121 | Drug Info | [24] | |||
| 3 | MM-141 | Drug Info | [25] | |||
| 4 | AMG888/U3-1287 | Drug Info | [26] | |||
| 5 | Anti-HER3/EGFR DAF | Drug Info | [22] | |||
| 6 | MM-151 | Drug Info | [25] | |||
| 7 | RG7116 | Drug Info | [36] | |||
| 8 | SYM-011 | Drug Info | [26] | |||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| 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 | Top | |||||
|---|---|---|---|---|---|---|
| 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 | ClinicalTrials.gov (NCT03321981) MCLA-128 With Trastuzumab/Chemotherapy in HER2+ and With Endocrine Therapy in ER+ and Low HER2 Breast Cancer. U.S. National Institutes of Health. | |||||
| REF 12 | Clinical pipeline report, company report or official report of Genentech (2011). | |||||
| REF 13 | 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 14 | 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 15 | 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 16 | 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 17 | ClinicalTrials.gov (NCT01957280) Study to Assess Pharmacokinetics, Immunogenicity and Safety/Tolerability of Patritumab (U3-1287). U.S. National Institutes of Health. | |||||
| REF 18 | Clinical pipeline report, company report or official report of Zensun. | |||||
| 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 800036915) | |||||
| REF 20 | 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 21 | ClinicalTrials.gov (NCT04603287) A Study of SI-B001, an EGFR/HER3 Bispecific Antibody, in Locally Advanced or Metastatic Epithelial Tumors. U.S. National Institutes of Health. | |||||
| REF 22 | Company report (Biooncology) | |||||
| REF 23 | Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801. | |||||
| REF 24 | Company report (Merrimack) | |||||
| REF 25 | 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 26 | 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 27 | 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 28 | Clinical pipeline report, company report or official report of Merus. | |||||
| REF 29 | 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 30 | National Cancer Institute Drug Dictionary (drug id 754219). | |||||
| REF 31 | Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36. | |||||
| REF 32 | 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 33 | 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 34 | Clinical pipeline report, company report or official report of Zensun. | |||||
| REF 35 | J Clin Oncol 32:5s, 2014 (suppl; abstr 2516). | |||||
| REF 36 | 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. | |||||
| REF 37 | Clinical pipeline report, company report or official report of SystImmune. | |||||
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