Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT308CBE)

• DOT Name: Interleukin-1 receptor antagonist protein (IL1RN)
• Synonyms: IL-1RN; IL-1ra; IRAP; ICIL-1RA; IL1 inhibitor; Anakinra
• Gene Name: IL1RN
• Related Disease: Sterile multifocal osteomyelitis with periostitis and pustulosis
• UniProt ID: IL1RA_HUMAN
• PDB ID: 1ILR; 1ILT; 1IRA; 1IRP; 2IRT
• Pfam ID: PF00340
• Sequence:
  MEICRGLRSHLITLLLFLFHSETICRPSGRKSSKMQAFRIWDVNQKTFYLRNNQLVAGYL
  QGPNVNLEEKIDVVPIEPHALFLGIHGGKMCLSCVKSGDETRLQLEAVNITDLSENRKQD
  KRFAFIRSDSGPTTSFESAACPGWFLCTAMEADQPVSLTNMPDEGVMVTKFYFQEDE
• Function: Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A. Protects from immune dysregulation and uncontrolled systemic inflammation triggered by IL1 for a range of innate stimulatory agents such as pathogens.
• Tissue Specificity: The intracellular form of IL1RN is predominantly expressed in epithelial cells.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)
• Reactome Pathway:
  Interleukin-1 signaling (R-HSA-9020702)
  Interleukin-10 signaling (R-HSA-6783783)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Sterile multifocal osteomyelitis with periostitis and pustulosis	DISP9B0B	Strong	Autosomal recessive	[1]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Isoproterenol	DMK7MEY	Approved	Interleukin-1 receptor antagonist protein (IL1RN) affects the response to substance of Isoproterenol.	[28]
Morphine	DMRMS0L	Approved	Interleukin-1 receptor antagonist protein (IL1RN) affects the response to substance of Morphine.	[29]
Acetylcholine	DMDF79Z	Approved	Interleukin-1 receptor antagonist protein (IL1RN) affects the response to substance of Acetylcholine.	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[11]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[11]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[13]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[11]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[11]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[15]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[11]
Methacholine Chloride	DMGS4QH	Approved	Methacholine Chloride increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[16]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[17]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[18]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[19]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[20]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[21]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[23]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[21]
Celastrol	DMWQIJX	Preclinical	Celastrol decreases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[25]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[26]
Alpha-naphthoflavone	DMELOIQ	Investigative	Alpha-naphthoflavone increases the expression of Interleukin-1 receptor antagonist protein (IL1RN).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the secretion of Interleukin-1 receptor antagonist protein (IL1RN).	[12]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the secretion of Interleukin-1 receptor antagonist protein (IL1RN).	[14]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the secretion of Interleukin-1 receptor antagonist protein (IL1RN).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interleukin-1 receptor antagonist protein (IL1RN).	[22]

References

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• [21] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
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