Target Information
| Target General Information | Top | |||||
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| Target ID |
T96788
(Former ID: TTDR01361)
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| Target Name |
ERBB2 messenger RNA (HER2 mRNA)
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| Synonyms |
Tyrosine kinase-type cell surface receptor HER2 (mRNA); Tyrosine kinase receptor ErbB2 (mRNA); Receptor tyrosine-protein kinase erbB-2 (mRNA); Proto-oncogene c-ErbB-2 (mRNA); Proto-oncogene Neu (mRNA); P185erbB2 (mRNA); NGL (mRNA); NEU proto-oncogene (mRNA); NEU (mRNA); Metastatic lymph node gene 19 protein (mRNA); MLN19 (mRNA); MLN 19 (mRNA); HER2/neu (mRNA); HER2 (erbB2/neu) (mRNA); HER-2 (mRNA); Erb2 (mRNA); Epidermal growth factor receptor 2 (mRNA); CD340 (mRNA); C-erbB-2 oncoprotein (mRNA); C-erbB-2 (mRNA)
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| Gene Name |
ERBB2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Breast cancer [ICD-11: 2C60-2C6Y] | |||||
| Function |
Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding.
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| BioChemical Class |
mRNA target
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| UniProt ID | ||||||
| EC Number |
EC 2.7.10.1
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| Sequence |
MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNL
ELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNG DPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLA LTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQC AAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACP YNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSAN IQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLP DLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTV PWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQEC VEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARC PSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVG ILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETEL RKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSP YVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR LVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFT HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWM IDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDA EEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEG AGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYV NQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQ GGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | HKI-272 | Drug Info | Phase 3 | Breast cancer | [2], [3] | |
| 2 | BMS-690514 | Drug Info | Phase 2 | Chronic pain | [4] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 21 Inhibitor drugs | + | ||||
| 1 | HKI-272 | Drug Info | [1] | |||
| 2 | BMS-690514 | Drug Info | [5] | |||
| 3 | (1-Benzyl-1H-indol-5-yl)-quinazolin-4-yl-amine | Drug Info | [6] | |||
| 4 | 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione | Drug Info | [7] | |||
| 5 | 3,4-diphenyl-1H-pyrrole-2,5-dione | Drug Info | [7] | |||
| 6 | 3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione | Drug Info | [7] | |||
| 7 | 3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione | Drug Info | [7] | |||
| 8 | 4-(3-phenoxylphenyl)-5-cyano-2H-1,2,3-triazole | Drug Info | [8] | |||
| 9 | 4-(4-bromophenyl)-5-cyano-2H-1,2,3-triazole | Drug Info | [8] | |||
| 10 | 4-(4-chlorophenyl)-5-cyano-2H-1,2,3-triazole | Drug Info | [8] | |||
| 11 | 4-(4-isopropylphenyl)-5-cyano-2H-1,2,3-triazole | Drug Info | [8] | |||
| 12 | 4-(Bis(2-chloroethyl)amino)-N-p-tolylbenzamide | Drug Info | [9] | |||
| 13 | AG-213 | Drug Info | [10] | |||
| 14 | BMS-536924 | Drug Info | [11] | |||
| 15 | CL-387785 | Drug Info | [12] | |||
| 16 | Geldanamycin-estradiol hybrid | Drug Info | [13] | |||
| 17 | HDS-029 | Drug Info | [12] | |||
| 18 | N-(4-m-Tolylamino-quinazolin-6-yl)-acrylamide | Drug Info | [15] | |||
| 19 | PD-168393 | Drug Info | [15] | |||
| 20 | PMID24915291C38 | Drug Info | [16] | |||
| 21 | PNT-500 | Drug Info | [17] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19936-41. | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021154) | |||||
| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | A novel epidermal growth factor receptor inhibitor promotes apoptosis in non-small cell lung cancer cells resistant to erlotinib. Cancer Res. 2007 Jul 1;67(13):6253-62. | |||||
| REF 5 | Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Aug;99(8):3579-93. | |||||
| REF 6 | Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2. Bioorg Med Chem Lett. 2001 Jun 4;11(11):1401-5. | |||||
| REF 7 | Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81. | |||||
| REF 8 | Synthesis and biological evaluation of 4-aryl-5-cyano-2H-1,2,3-triazoles as inhibitor of HER2 tyrosine kinase. Bioorg Med Chem. 2007 Feb 1;15(3):1533-8. | |||||
| REF 9 | Synthesis, biological evaluation and molecular docking studies of amide-coupled benzoic nitrogen mustard derivatives as potential antitumor agents. Bioorg Med Chem. 2010 Jan 15;18(2):880-6. | |||||
| REF 10 | Syntheses of 4-(indole-3-yl)quinazolines: a new class of epidermal growth factor receptor tyrosine kinase inhibitors. Eur J Med Chem. 2008 Jul;43(7):1478-88. | |||||
| REF 11 | Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43. | |||||
| REF 12 | Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB... J Med Chem. 2006 Feb 23;49(4):1475-85. | |||||
| REF 13 | Synthesis and evaluation of geldanamycin-estradiol hybrids. Bioorg Med Chem Lett. 1999 May 3;9(9):1233-8. | |||||
| REF 14 | US patent application no. 5,968,748, Antisense oligonucleotide modulation of human HER-2 expression. | |||||
| REF 15 | Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP... J Med Chem. 1999 May 20;42(10):1803-15. | |||||
| REF 16 | Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem. 2014 Jun 26;57(12):5112-28. | |||||
| REF 17 | 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: 2019). | |||||
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