Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRSST0A)

• DOT Name: Receptor tyrosine-protein kinase erbB-3 (ERBB3)
• Synonyms: EC 2.7.10.1; Proto-oncogene-like protein c-ErbB-3; Tyrosine kinase-type cell surface receptor HER3
• Gene Name: ERBB3
• Related Disease:
  Lethal congenital contracture syndrome 2
  Hirschsprung disease
• UniProt ID: ERBB3_HUMAN
• PDB ID: 1M6B; 2L9U; 3KEX; 3LMG; 3P11; 4LEO; 4P59; 4RIW; 4RIX; 4RIY; 5CUS; 5O4O; 5O7P; 6KBI; 6OP9; 7BHE; 7BHF; 7D85; 7MN5; 7MN6; 7MN8
• EC Number: 2.7.10.1
• Pfam ID: PF00757 ; PF14843 ; PF07714 ; PF01030
• 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: Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. 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.
• Tissue Specificity: Epithelial tissues and brain.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  MAPK sig.ling pathway (hsa04010)
  ErbB sig.ling pathway (hsa04012)
  Calcium sig.ling pathway (hsa04020)
  PI3K-Akt sig.ling pathway (hsa04151)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lethal congenital contracture syndrome 2	DISN4BL3	Strong	Autosomal recessive	[1]
Hirschsprung disease	DISUUSM1	Supportive	Autosomal dominant	[2]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Receptor tyrosine-protein kinase erbB-3 (ERBB3) decreases the response to substance of Paclitaxel.	[29]
Mitomycin	DMH0ZJE	Approved	Receptor tyrosine-protein kinase erbB-3 (ERBB3) affects the response to substance of Mitomycin.	[30]
Topotecan	DMP6G8T	Approved	Receptor tyrosine-protein kinase erbB-3 (ERBB3) affects the response to substance of Topotecan.	[30]
Capecitabine	DMTS85L	Approved	Receptor tyrosine-protein kinase erbB-3 (ERBB3) increases the response to substance of Capecitabine.	[29]

35 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-3 (ERBB3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[10]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[13]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[14]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[6]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[6]
Lapatinib	DM3BH1Y	Approved	Lapatinib decreases the activity of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[16]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[17]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[18]
EXISULIND	DMBY56U	Phase 3	EXISULIND decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[18]
GDC0941	DM1YAK6	Phase 2	GDC0941 increases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[19]
GDC-0980/RG7422	DMF3MV1	Phase 2	GDC-0980/RG7422 increases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[20]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[24]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[25]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[26]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[14]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE decreases the expression of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[27]
PD-158780	DMQXYE9	Investigative	PD-158780 decreases the activity of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[28]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Receptor tyrosine-protein kinase erbB-3 (ERBB3).	[21]

References

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