Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOAUNCK)

DOT Name Receptor tyrosine-protein kinase erbB-2 (ERBB2)
Synonyms EC 2.7.10.1; Metastatic lymph node gene 19 protein; MLN 19; Proto-oncogene Neu; Proto-oncogene c-ErbB-2; Tyrosine kinase-type cell surface receptor HER2; p185erbB2; CD antigen CD340
Gene Name ERBB2
Related Disease
Hirschsprung disease ( )
Glioma susceptibility 1 ( )
Lung cancer ( )
Visceral neuropathy, familial, 2, autosomal recessive ( )
UniProt ID
ERBB2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1MFG ; 1MFL ; 1MW4 ; 1N8Z ; 1QR1 ; 1S78 ; 2A91 ; 2JWA ; 2KS1 ; 2L4K ; 2N2A ; 3BE1 ; 3H3B ; 3MZW ; 3N85 ; 3PP0 ; 3RCD ; 3WLW ; 3WSQ ; 4GFU ; 4HRL ; 4HRM ; 4HRN ; 4NND ; 5K33 ; 5KWG ; 5MY6 ; 5O4G ; 5OB4 ; 5TQS ; 6ATT ; 6BGT ; 6J71 ; 6LBX ; 6OGE ; 7JXH ; 7MN5 ; 7MN6 ; 7MN8 ; 7PCD ; 7QVK ; 8FFJ ; 8HGO ; 8HGP ; 8Q6J
EC Number
2.7.10.1
Pfam ID
PF00757 ; PF14843 ; PF07714 ; PF01030 ; PF21314
Sequence
MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNL
ELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNG
DPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLA
LTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQC
AAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACP
YNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSAN
IQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLP
DLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTV
PWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQEC
VEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARC
PSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVG
ILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETEL
RKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSP
YVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR
LVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFT
HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWM
IDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDA
EEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEG
AGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYV
NQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQ
GGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV
Function
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. 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; In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.
Tissue Specificity Expressed in a variety of tumor tissues including primary breast tumors and tumors from small bowel, esophagus, kidney and mouth.
KEGG Pathway
EGFR tyrosine ki.se inhibitor resistance (hsa01521 )
Endocrine resistance (hsa01522 )
Platinum drug resistance (hsa01524 )
MAPK sig.ling pathway (hsa04010 )
ErbB sig.ling pathway (hsa04012 )
Calcium sig.ling pathway (hsa04020 )
HIF-1 sig.ling pathway (hsa04066 )
PI3K-Akt sig.ling pathway (hsa04151 )
Focal adhesion (hsa04510 )
Adherens junction (hsa04520 )
Tight junction (hsa04530 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
MicroR.s in cancer (hsa05206 )
Pancreatic cancer (hsa05212 )
Endometrial cancer (hsa05213 )
Prostate cancer (hsa05215 )
Bladder cancer (hsa05219 )
Non-small cell lung cancer (hsa05223 )
Breast cancer (hsa05224 )
Gastric cancer (hsa05226 )
Central carbon metabolism in cancer (hsa05230 )
Reactome Pathway
SHC1 events in ERBB2 signaling (R-HSA-1250196 )
PLCG1 events in ERBB2 signaling (R-HSA-1251932 )
PIP3 activates AKT signaling (R-HSA-1257604 )
GRB7 events in ERBB2 signaling (R-HSA-1306955 )
Downregulation of ERBB2 (R-HSA-1358803 )
GRB2 events in ERBB2 signaling (R-HSA-1963640 )
PI3K events in ERBB2 signaling (R-HSA-1963642 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
Sema4D induced cell migration and growth-cone collapse (R-HSA-416572 )
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 )
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors (R-HSA-8866910 )
Constitutive Signaling by Overexpressed ERBB2 (R-HSA-9634285 )
Drug-mediated inhibition of ERBB2 signaling (R-HSA-9652282 )
Signaling by ERBB2 KD Mutants (R-HSA-9664565 )
Resistance of ERBB2 KD mutants to trastuzumab (R-HSA-9665233 )
Resistance of ERBB2 KD mutants to sapitinib (R-HSA-9665244 )
Resistance of ERBB2 KD mutants to tesevatinib (R-HSA-9665245 )
Resistance of ERBB2 KD mutants to neratinib (R-HSA-9665246 )
Resistance of ERBB2 KD mutants to osimertinib (R-HSA-9665247 )
Resistance of ERBB2 KD mutants to afatinib (R-HSA-9665249 )
Resistance of ERBB2 KD mutants to AEE788 (R-HSA-9665250 )
Resistance of ERBB2 KD mutants to lapatinib (R-HSA-9665251 )
Signaling by ERBB2 ECD mutants (R-HSA-9665348 )
Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686 )
Drug resistance in ERBB2 TMD/JMD mutants (R-HSA-9665737 )
Signaling by ERBB2 (R-HSA-1227986 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hirschsprung disease DISUUSM1 Supportive Autosomal dominant [1]
Glioma susceptibility 1 DISD5L1R Limited Unknown [2]
Lung cancer DISCM4YA Limited Autosomal dominant [3]
Visceral neuropathy, familial, 2, autosomal recessive DISHTNFX Limited Unknown [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 12 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Fluorouracil DMUM7HZ Approved Receptor tyrosine-protein kinase erbB-2 (ERBB2) decreases the response to substance of Fluorouracil. [61]
Paclitaxel DMLB81S Approved Receptor tyrosine-protein kinase erbB-2 (ERBB2) decreases the response to substance of Paclitaxel. [62]
Gemcitabine DMSE3I7 Approved Receptor tyrosine-protein kinase erbB-2 (ERBB2) increases the Fatigue ADR of Gemcitabine. [63]
Mitoxantrone DMM39BF Approved Receptor tyrosine-protein kinase erbB-2 (ERBB2) decreases the response to substance of Mitoxantrone. [64]
Vinblastine DM5TVS3 Approved Receptor tyrosine-protein kinase erbB-2 (ERBB2) affects the response to substance of Vinblastine. [65]
Docetaxel DMDI269 Approved Receptor tyrosine-protein kinase erbB-2 (ERBB2) increases the response to substance of Docetaxel. [66]
Thiotepa DMIZKOP Approved Receptor tyrosine-protein kinase erbB-2 (ERBB2) affects the response to substance of Thiotepa. [65]
Trastuzumab DMZQOUX Approved Receptor tyrosine-protein kinase erbB-2 (ERBB2) increases the Neoplasm related morbidities ADR of Trastuzumab. [63]
GDC0941 DM1YAK6 Phase 2 Receptor tyrosine-protein kinase erbB-2 (ERBB2) increases the response to substance of GDC0941. [67]
TAK165 DMBE5OF Discontinued in Phase 1 Receptor tyrosine-protein kinase erbB-2 (ERBB2) affects the response to substance of TAK165. [68]
Paraquat DMR8O3X Investigative Receptor tyrosine-protein kinase erbB-2 (ERBB2) decreases the response to substance of Paraquat. [69]
DEMETHOXYCURCUMIN DMO5UGV Investigative Receptor tyrosine-protein kinase erbB-2 (ERBB2) increases the response to substance of DEMETHOXYCURCUMIN. [70]
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⏷ Show the Full List of 12 Drug(s)
55 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [4]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [5]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [7]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [9]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [10]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [11]
Quercetin DM3NC4M Approved Quercetin increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [12]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [13]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [14]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [15]
Carbamazepine DMZOLBI Approved Carbamazepine decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [16]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [17]
Selenium DM25CGV Approved Selenium increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [18]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [11]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [19]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [21]
Aspirin DM672AH Approved Aspirin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [22]
Etoposide DMNH3PG Approved Etoposide decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [23]
Permethrin DMZ0Q1G Approved Permethrin increases the activity of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [24]
Capsaicin DMGMF6V Approved Capsaicin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [25]
Lindane DMB8CNL Approved Lindane increases the activity of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [24]
Orlistat DMRJSP8 Approved Orlistat decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [27]
Romidepsin DMT5GNL Approved Romidepsin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [28]
Mechlorethamine DM0CVXA Approved Mechlorethamine decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [29]
Dutasteride DMQ4TJK Approved Dutasteride increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [30]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [32]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [33]
Curcumin DMQPH29 Phase 3 Curcumin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [35]
Chloroquine DMSI5CB Phase 3 Trial Chloroquine decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [37]
Napabucasin DMDZ6Q3 Phase 3 Napabucasin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [38]
EXISULIND DMBY56U Phase 3 EXISULIND decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [37]
Afimoxifene DMFORDT Phase 2 Afimoxifene decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [11]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [39]
Tanespimycin DMNLQHK Phase 2 Tanespimycin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [40]
BAICALEIN DM4C7E6 Phase 2 BAICALEIN decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [41]
MK-2206 DMT1OZ6 Phase 2 MK-2206 increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [42]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [44]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [45]
LY294002 DMY1AFS Phase 1 LY294002 decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [46]
Tetrandrine DMAOJBX Phase 1 Tetrandrine decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [47]
PMID26882240-Compound-32 DMJS4RP Patented PMID26882240-Compound-32 decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [40]
Geldanamycin DMS7TC5 Discontinued in Phase 2 Geldanamycin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [49]
PKI166 DMSQ794 Discontinued in Phase 2 PKI166 decreases the activity of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [50]
MG-132 DMKA2YS Preclinical MG-132 decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [51]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [52]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [54]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [14]
Nitrobenzanthrone DMN6L70 Investigative Nitrobenzanthrone decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [55]
Cycloheximide DMGDA3C Investigative Cycloheximide decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [11]
Cordycepin DM72Y01 Investigative Cordycepin decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [56]
N-nonylphenol DMH3OUX Investigative N-nonylphenol decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [57]
RHEIN DMS6IJ0 Investigative RHEIN decreases the expression of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [58]
PD-158780 DMQXYE9 Investigative PD-158780 decreases the activity of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [60]
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⏷ Show the Full List of 55 Drug(s)
9 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bortezomib DMNO38U Approved Bortezomib decreases the phosphorylation of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [20]
Gefitinib DM15F0X Approved Gefitinib decreases the phosphorylation of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [26]
Amiloride DMRTSGP Approved Amiloride decreases the phosphorylation of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [31]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate decreases the phosphorylation of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [34]
Rigosertib DMOSTXF Phase 3 Rigosertib increases the phosphorylation of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [36]
Delphinidin DMS2WIN Phase 2 Delphinidin decreases the phosphorylation of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [34]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [48]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the phosphorylation of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [53]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [48]
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⏷ Show the Full List of 9 Drug(s)
2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Trastuzumab Emtansine DMU1LXS Phase 2 Trastuzumab Emtansine affects the binding of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [43]
PALMATINE DMJCOKV Investigative PALMATINE affects the binding of Receptor tyrosine-protein kinase erbB-2 (ERBB2). [59]
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