Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3F9IR2)

• DOT Name: Nuclear receptor subfamily 4 group A member 2 (NR4A2)
• Synonyms: Immediate-early response protein NOT; Orphan nuclear receptor NURR1; Transcriptionally-inducible nuclear receptor
• Gene Name: NR4A2
• Related Disease:
  Complex neurodevelopmental disorder
  Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism
• UniProt ID: NR4A2_HUMAN
• PDB ID: 1OVL; 5Y41; 5YD6; 6DDA; 6L6L; 6L6Q; 7WNH
• Pfam ID: PF00104 ; PF00105
• Sequence:
  MPCVQAQYGSSPQGASPASQSYSYHSSGEYSSDFLTPEFVKFSMDLTNTEITATTSLPSF
  STFMDNYSTGYDVKPPCLYQMPLSGQQSSIKVEDIQMHNYQQHSHLPPQSEEMMPHSGSV
  YYKPSSPPTPTTPGFQVQHSPMWDDPGSLHNFHQNYVATTHMIEQRKTPVSRLSLFSFKQ
  SPPGTPVSSCQMRFDGPLHVPMNPEPAGSHHVVDGQTFAVPNPIRKPASMGFPGLQIGHA
  SQLLDTQVPSPPSRGSPSNEGLCAVCGDNAACQHYGVRTCEGCKGFFKRTVQKNAKYVCL
  ANKNCPVDKRRRNRCQYCRFQKCLAVGMVKEVVRTDSLKGRRGRLPSKPKSPQEPSPPSP
  PVSLISALVRAHVDSNPAMTSLDYSRFQANPDYQMSGDDTQHIQQFYDLLTGSMEIIRGW
  AEKIPGFADLPKADQDLLFESAFLELFVLRLAYRSNPVEGKLIFCNGVVLHRLQCVRGFG
  EWIDSIVEFSSNLQNMNIDISAFSCIAALAMVTERHGLKEPKRVEELQNKIVNCLKDHVT
  FNNGGLNRPNYLSKLLGKLPELRTLCTQGLQRIFYLKLEDLVPPPAIIDKLFLDTLPF
• Function: Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons.
• Tissue Specificity: Expressed in a number of cell lines of T-cell, B-cell and fibroblast origin. Strong expression in brain tissue.
• KEGG Pathway:
  Aldosterone synthesis and secretion (hsa04925)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
• Reactome Pathway:
  SUMOylation of intracellular receptors (R-HSA-4090294)
  Nuclear Receptor transcription pathway (R-HSA-383280)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Definitive	Autosomal dominant	[1]
Intellectual developmental disorder with language impairment and early-onset DOPA-responsive dystonia-parkinsonism	DISKXKK2	Strong	Autosomal dominant	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Nuclear receptor subfamily 4 group A member 2 (NR4A2) affects the response to substance of Mitoxantrone.	[42]

38 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 Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[14]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[15]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[16]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[18]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[19]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[20]
Capecitabine	DMTS85L	Approved	Capecitabine decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[21]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[22]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[23]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[24]
Dalcetrapib	DMKNCVM	Phase 3	Dalcetrapib increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[25]
Anacetrapib	DMP2BFG	Phase 3	Anacetrapib increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[25]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[26]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[27]
Lithium	DMZ3OU6	Phase 2	Lithium increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[28]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[29]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[31]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[32]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[34]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[35]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[36]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[37]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[38]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[39]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[40]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[41]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Permethrin	DMZ0Q1G	Approved	Permethrin affects the binding of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Nuclear receptor subfamily 4 group A member 2 (NR4A2).	[33]

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