Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGP6GA4)

• DOT Name: Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1)
• Synonyms: Early response protein NAK1; Nuclear hormone receptor NUR/77; Nur77; Orphan nuclear receptor HMR; Orphan nuclear receptor TR3; ST-59; Testicular receptor 3
• Gene Name: NR4A1
• UniProt ID: NR4A1_HUMAN
• PDB ID: 2QW4; 3V3E; 3V3Q; 4JGV; 4KZI; 4KZJ; 4KZM; 4RE8; 4REE; 4REF; 4RZE; 4RZF; 4RZG; 4WHF; 4WHG; 6KZ5; 6LC1
• Pfam ID: PF00104 ; PF00105
• Sequence:
  MPCIQAQYGTPAPSPGPRDHLASDPLTPEFIKPTMDLASPEAAPAAPTALPSFSTFMDGY
  TGEFDTFLYQLPGTVQPCSSASSSASSTSSSSATSPASASFKFEDFQVYGCYPGPLSGPV
  DEALSSSGSDYYGSPCSAPSPSTPSFQPPQLSPWDGSFGHFSPSQTYEGLRAWTEQLPKA
  SGPPQPPAFFSFSPPTGPSPSLAQSPLKLFPSQATHQLGEGESYSMPTAFPGLAPTSPHL
  EGSGILDTPVTSTKARSGAPGGSEGRCAVCGDNASCQHYGVRTCEGCKGFFKRTVQKNAK
  YICLANKDCPVDKRRRNRCQFCRFQKCLAVGMVKEVVRTDSLKGRRGRLPSKPKQPPDAS
  PANLLTSLVRAHLDSGPSTAKLDYSKFQELVLPHFGKEDAGDVQQFYDLLSGSLEVIRKW
  AEKIPGFAELSPADQDLLLESAFLELFILRLAYRSKPGEGKLIFCSGLVLHRLQCARGFG
  DWIDSILAFSRSLHSLLVDVPAFACLSALVLITDRHGLQEPRRVEELQNRIASCLKEHVA
  AVAGEPQPASCLSRLLGKLPELRTLCTQGLQRIFYLKLEDLVPPPPIIDKIFMDTLPF
• Function: Orphan nuclear receptor. Binds the NGFI-B response element (NBRE) 5'-AAAGGTCA-3'. Binds 9-cis-retinoic acid outside of its ligand-binding (NR LBD) domain. Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation. Regulates the inflammatory response in macrophages by regulating metabolic adaptations during inflammation, including repressing the transcription of genes involved in the citric acid cycle (TCA). Inhibits NF-kappa-B signaling by binding to low-affinity NF-kappa-B binding sites, such as at the IL2 promoter. May act concomitantly with NR4A2 in regulating the expression of delayed-early genes during liver regeneration. Plays a role in the vascular response to injury; In the cytosol, upon its detection of both bacterial lipopolysaccharide (LPS) and NBRE-containing mitochondrial DNA released by GSDMD pores during pyroptosis, it promotes non-canonical NLRP3 inflammasome activation by stimulating association of NLRP3 and NEK7.
• Tissue Specificity: Fetal muscle and adult liver, brain and thyroid.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  PI3K-Akt sig.ling pathway (hsa04151)
  Aldosterone synthesis and secretion (hsa04925)
  Cortisol synthesis and secretion (hsa04927)
  Cushing syndrome (hsa04934)
• Reactome Pathway:
  Nuclear Receptor transcription pathway (R-HSA-383280)
  Constitutive Signaling by AKT1 E17K in Cancer (R-HSA-5674400)
  AKT phosphorylates targets in the nucleus (R-HSA-198693)

Molecular Interaction Atlas (MIA) of This DOT

41 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[11]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[12]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[13]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[14]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[15]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[16]
Capecitabine	DMTS85L	Approved	Capecitabine decreases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[17]
Febuxostat	DMDEXQ0	Approved	Febuxostat increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[18]
Potassium chloride	DMMTAJC	Approved	Potassium chloride increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[20]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[21]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[22]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[23]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[6]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[26]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[27]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[28]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[29]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[31]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[32]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[33]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[34]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[35]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[36]
Fenthion	DMKEG49	Investigative	Fenthion increases the expression of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1).	[30]

References

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