Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4VUWH1)

• DOT Name: Interleukin-24 (IL24)
• Synonyms: IL-24; Melanoma differentiation-associated gene 7 protein; MDA-7; Suppression of tumorigenicity 16 protein
• Gene Name: IL24
• UniProt ID: IL24_HUMAN
• PDB ID: 6DF3; 6GG1
• Sequence:
  MNFQQRLQSLWTLARPFCPPLLATASQMQMVVLPCLGFTLLLWSQVSGAQGQEFHFGPCQ
  VKGVVPQKLWEAFWAVKDTMQAQDNITSARLLQQEVLQNVSDAESCYLVHTLLEFYLKTV
  FKNYHNRTVEVRTLKSFSTLANNFVLIVSQLQPSQENEMFSIRDSAHRRFLLFRRAFKQL
  DVEAALTKALGEVDILLTWMQKFYKL
• Function: Multifunctional cytokine mainly produced by T-cells that plays a regulatory role in immune response, tissue homeostasis, host defense, and oncogenesis. Possesses antiviral functions and induces the type I interferon response during influenza infection. Signals through two receptor complexes IL20RA/IL20RB or IL20RB/IL22RA1. In turn, stimulates the JAK1-STAT3 and MAPK pathways and promotes the secretion of pro-inflammatory mediators including IL8 and MMP1. Intracellularly, maintains endoplasmic reticulum homeostasis by restricting the eIF2alpha-CHOP pathway-mediated stress signal. In addition, acts as a quality control mechanism for the ubiquitin proteasome system by alerting the cell to proteasome dysfunction through activation of PKR/EIF2AK2.
• Tissue Specificity: Up-regulated in melanoma cells induced to terminally differentiate.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: Interleukin-20 family signaling (R-HSA-8854691)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Interleukin-24 (IL24) increases the response to substance of Temozolomide.	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Interleukin-24 (IL24).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the activity of Interleukin-24 (IL24).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interleukin-24 (IL24).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interleukin-24 (IL24).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Interleukin-24 (IL24).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Interleukin-24 (IL24).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the activity of Interleukin-24 (IL24).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Interleukin-24 (IL24).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Interleukin-24 (IL24).	[8]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Interleukin-24 (IL24).	[9]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Interleukin-24 (IL24).	[5]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Interleukin-24 (IL24).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Interleukin-24 (IL24).	[3]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Interleukin-24 (IL24).	[11]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Interleukin-24 (IL24).	[12]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Interleukin-24 (IL24).	[12]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Interleukin-24 (IL24).	[13]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Interleukin-24 (IL24).	[14]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Interleukin-24 (IL24).	[15]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Interleukin-24 (IL24).	[16]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Interleukin-24 (IL24).	[3]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Interleukin-24 (IL24).	[17]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Interleukin-24 (IL24).	[12]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Interleukin-24 (IL24).	[12]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Interleukin-24 (IL24).	[12]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Interleukin-24 (IL24).	[12]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Interleukin-24 (IL24).	[12]
Isoniazid	DM5JVS3	Approved	Isoniazid increases the expression of Interleukin-24 (IL24).	[12]
Mebendazole	DMO14SG	Approved	Mebendazole increases the expression of Interleukin-24 (IL24).	[12]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Interleukin-24 (IL24).	[12]
Clavulanate	DM2FGRT	Approved	Clavulanate decreases the expression of Interleukin-24 (IL24).	[12]
Flutamide	DMK0O7U	Approved	Flutamide increases the expression of Interleukin-24 (IL24).	[12]
Etodolac	DM6WJO9	Approved	Etodolac increases the expression of Interleukin-24 (IL24).	[12]
Salbutamol	DMN9CWF	Approved	Salbutamol increases the expression of Interleukin-24 (IL24).	[12]
Tolcapone	DM8MNVO	Approved	Tolcapone decreases the expression of Interleukin-24 (IL24).	[12]
Zafirlukast	DMHNQOG	Approved	Zafirlukast increases the expression of Interleukin-24 (IL24).	[12]
Trazodone	DMK1GBJ	Approved	Trazodone increases the expression of Interleukin-24 (IL24).	[12]
Primaquine	DMWQ16I	Approved	Primaquine decreases the expression of Interleukin-24 (IL24).	[12]
Amikacin	DM5PDRB	Approved	Amikacin decreases the expression of Interleukin-24 (IL24).	[12]
Phentolamine	DMXYJOB	Approved	Phentolamine decreases the expression of Interleukin-24 (IL24).	[12]
Lumiracoxib	DM1S4AG	Approved	Lumiracoxib increases the expression of Interleukin-24 (IL24).	[12]
Trihexyphenidyl	DMB19L8	Approved	Trihexyphenidyl increases the expression of Interleukin-24 (IL24).	[12]
Procyclidine	DMHFJDT	Approved	Procyclidine increases the expression of Interleukin-24 (IL24).	[12]
Penbutolol	DM4ES8F	Approved	Penbutolol increases the expression of Interleukin-24 (IL24).	[12]
Aciclovir	DMYLOVR	Approved	Aciclovir increases the expression of Interleukin-24 (IL24).	[12]
Primidone	DM0WX6I	Approved	Primidone increases the expression of Interleukin-24 (IL24).	[12]
Phenoxybenzamine	DM8KSQH	Approved	Phenoxybenzamine decreases the expression of Interleukin-24 (IL24).	[12]
Levofloxacin	DMS60RB	Approved	Levofloxacin increases the expression of Interleukin-24 (IL24).	[12]
Paliperidone	DM7NPJS	Approved	Paliperidone increases the expression of Interleukin-24 (IL24).	[12]
Biperiden	DME78OA	Approved	Biperiden increases the expression of Interleukin-24 (IL24).	[12]
Didanosine	DMI2QPE	Approved	Didanosine decreases the expression of Interleukin-24 (IL24).	[12]
Diphenhydramine	DMKQTBA	Approved	Diphenhydramine decreases the expression of Interleukin-24 (IL24).	[12]
Alpidem	DMN7Y9K	Approved	Alpidem increases the expression of Interleukin-24 (IL24).	[12]
Aminosalicylic acid	DMENSL5	Approved	Aminosalicylic acid increases the expression of Interleukin-24 (IL24).	[12]
Pirprofen	DMMOFHT	Approved	Pirprofen increases the expression of Interleukin-24 (IL24).	[12]
Protriptyline	DMNHTZI	Approved	Protriptyline increases the expression of Interleukin-24 (IL24).	[12]
Hydroxyzine	DMF8Y74	Approved	Hydroxyzine increases the expression of Interleukin-24 (IL24).	[12]
Minoxidil	DMA2Z4F	Approved	Minoxidil decreases the expression of Interleukin-24 (IL24).	[12]
Metronidazole	DMTIVEN	Approved	Metronidazole increases the expression of Interleukin-24 (IL24).	[12]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Interleukin-24 (IL24).	[18]
EXISULIND	DMBY56U	Phase 3	EXISULIND increases the expression of Interleukin-24 (IL24).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-24 (IL24).	[20]
Nomifensine	DMCP2TS	Withdrawn from market	Nomifensine increases the expression of Interleukin-24 (IL24).	[12]
Nimesulide	DMR1NMD	Terminated	Nimesulide increases the expression of Interleukin-24 (IL24).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interleukin-24 (IL24).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Interleukin-24 (IL24).	[22]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Interleukin-24 (IL24).	[23]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Interleukin-24 (IL24).	[24]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Interleukin-24 (IL24).	[25]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Interleukin-24 (IL24).	[3]
Hydroxydimethylarsine Oxide	DMPS2B1	Investigative	Hydroxydimethylarsine Oxide increases the expression of Interleukin-24 (IL24).	[26]
PK 11195	DMDOZPU	Investigative	PK 11195 increases the activity of Interleukin-24 (IL24).	[2]
IPRONIAZIDE	DM42ENF	Investigative	IPRONIAZIDE increases the expression of Interleukin-24 (IL24).	[12]
Oxybutynine	DMJPBAX	Investigative	Oxybutynine decreases the expression of Interleukin-24 (IL24).	[12]
bongkrek acid	DMWALXQ	Investigative	bongkrek acid decreases the activity of Interleukin-24 (IL24).	[2]

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 decreases the methylation of Interleukin-24 (IL24).	[19]

References

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• [14] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
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• [23] Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells. J Appl Toxicol. 2007 Jan-Feb;27(1):67-77. doi: 10.1002/jat.1200.
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