Details of Drug Off-Target (DOT)

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

• DOT Name: Interleukin-4 (IL4)
• Synonyms: IL-4; B-cell stimulatory factor 1; BSF-1; Binetrakin; Lymphocyte stimulatory factor 1; Pitrakinra
• Gene Name: IL4
• UniProt ID: IL4_HUMAN
• PDB ID: 1BBN; 1BCN; 1CYL; 1HIJ; 1HIK; 1HZI; 1IAR; 1ITI; 1ITL; 1ITM; 1RCB; 2B8U; 2B8X; 2B8Y; 2B8Z; 2B90; 2B91; 2CYK; 2D48; 2INT; 3BPL; 3BPN; 3QB7; 4YDY; 5FHX; 6OEL; 8A4F; 8CGF; 8CH7
• Pfam ID: PF00727
• Sequence:
  MGLTSQLLPPLFFLLACAGNFVHGHKCDITLQEIIKTLNSLTEQKTLCTELTVTDIFAAS
  KNTTEKETFCRAATVLRQFYSHHEKDTRCLGATAQQFHRHKQLIRFLKRLDRNLWGLAGL
  NSCPVKEANQSTLENFLERLKTIMREKYSKCSS
• Function: Cytokine secreted primarily by mast cells, T-cells, eosinophils, and basophils that plays a role in regulating antibody production, hematopoiesis and inflammation, and the development of effector T-cell responses. Induces the expression of class II MHC molecules on resting B-cells. Enhances both secretion and cell surface expression of IgE and IgG1. Regulates also the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages. Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4. In addition, plays a critical role in higher functions of the normal brain, such as memory and learning. Upon binding to IL4, IL4R receptor dimerizes either with the common IL2R gamma chain/IL2RG to produce the type 1 signaling complex, located mainly on hematopoietic cells, or with the IL13RA1 to produce the type 2 complex, which is expressed also on nonhematopoietic cells. Engagement of both types of receptors initiates JAK3 and to a lower extend JAK1 phosphorylation leading to activation of the signal transducer and activator of transcription 6/STAT6.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt sig.ling pathway (hsa04151)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  IL-17 sig.ling pathway (hsa04657)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  T cell receptor sig.ling pathway (hsa04660)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Intesti.l immune network for IgA production (hsa04672)
  Leishmaniasis (hsa05140)
  Pathways in cancer (hsa05200)
  Asthma (hsa05310)
  Autoimmune thyroid disease (hsa05320)
  Inflammatory bowel disease (hsa05321)
  Allograft rejection (hsa05330)
• Reactome Pathway:
  Interleukin-18 signaling (R-HSA-9012546)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Interleukin-4 (IL4) decreases the response to substance of Etoposide.	[51]
Diclofenac	DMPIHLS	Approved	Interleukin-4 (IL4) increases the response to substance of Diclofenac.	[52]
Abacavir	DMMN36E	Approved	Interleukin-4 (IL4) affects the response to substance of Abacavir.	[53]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
PGF2alpha	DM4XAU7	Clinical trial	Interleukin-4 (IL4) increases the secretion of PGF2alpha.	[54]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]cAMP	DMZRQU7	Investigative	Interleukin-4 (IL4) increases the chemical synthesis of [3H]cAMP.	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Interleukin-4 (IL4).	[1]
Azacitidine	DMTA5OE	Approved	Azacitidine affects the methylation of Interleukin-4 (IL4).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interleukin-4 (IL4).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interleukin-4 (IL4).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-4 (IL4).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interleukin-4 (IL4).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Interleukin-4 (IL4).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Interleukin-4 (IL4).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Interleukin-4 (IL4).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interleukin-4 (IL4).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Interleukin-4 (IL4).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Interleukin-4 (IL4).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-4 (IL4).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Interleukin-4 (IL4).	[10]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Interleukin-4 (IL4).	[11]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Interleukin-4 (IL4).	[12]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Interleukin-4 (IL4).	[15]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Interleukin-4 (IL4).	[16]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Interleukin-4 (IL4).	[17]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interleukin-4 (IL4).	[18]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Interleukin-4 (IL4).	[19]
Isoproterenol	DMK7MEY	Approved	Isoproterenol decreases the expression of Interleukin-4 (IL4).	[21]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of Interleukin-4 (IL4).	[22]
Morphine	DMRMS0L	Approved	Morphine increases the expression of Interleukin-4 (IL4).	[23]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the expression of Interleukin-4 (IL4).	[24]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR decreases the expression of Interleukin-4 (IL4).	[25]
Salicyclic acid	DM2F8XZ	Approved	Salicyclic acid decreases the expression of Interleukin-4 (IL4).	[12]
Prednisone	DM2HG4X	Approved	Prednisone decreases the expression of Interleukin-4 (IL4).	[11]
Terbinafine	DMI6HUW	Approved	Terbinafine decreases the expression of Interleukin-4 (IL4).	[26]
Cladribine	DM3JDRP	Approved	Cladribine increases the expression of Interleukin-4 (IL4).	[28]
Miconazole	DMPMYE8	Approved	Miconazole decreases the expression of Interleukin-4 (IL4).	[26]
Methadone	DMTW6IU	Approved	Methadone increases the expression of Interleukin-4 (IL4).	[23]
Clarithromycin	DM4M1SG	Approved	Clarithromycin decreases the expression of Interleukin-4 (IL4).	[25]
Fentanyl	DM8WAHT	Approved	Fentanyl increases the expression of Interleukin-4 (IL4).	[23]
Dydrogesterone	DMAKIDV	Approved	Dydrogesterone increases the expression of Interleukin-4 (IL4).	[29]
Itraconazole	DMCR1MV	Approved	Itraconazole decreases the expression of Interleukin-4 (IL4).	[26]
Betamethasone valerate	DMMIAXO	Approved	Betamethasone valerate decreases the expression of Interleukin-4 (IL4).	[24]
Buprenorphine	DMPRI8G	Approved	Buprenorphine increases the expression of Interleukin-4 (IL4).	[23]
Tolnaftate	DM28MU7	Approved	Tolnaftate decreases the expression of Interleukin-4 (IL4).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Interleukin-4 (IL4).	[30]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Interleukin-4 (IL4).	[31]
Sodium stibogluconate	DMH5MVE	Phase 2	Sodium stibogluconate decreases the expression of Interleukin-4 (IL4).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-4 (IL4).	[34]
Ribavirin	DMEYLH9	Phase 1 Trial	Ribavirin decreases the expression of Interleukin-4 (IL4).	[35]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Interleukin-4 (IL4).	[9]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 decreases the expression of Interleukin-4 (IL4).	[36]
JWH-015	DMGTSCP	Patented	JWH-015 increases the expression of Interleukin-4 (IL4).	[37]
Terfenadine	DM4KLPT	Withdrawn from market	Terfenadine decreases the expression of Interleukin-4 (IL4).	[38]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Interleukin-4 (IL4).	[41]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos decreases the expression of Interleukin-4 (IL4).	[42]
Aminohippuric acid	DMUN54G	Investigative	Aminohippuric acid increases the expression of Interleukin-4 (IL4).	[43]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of Interleukin-4 (IL4).	[45]
Apigenin	DMI3491	Investigative	Apigenin decreases the expression of Interleukin-4 (IL4).	[36]
3,7,3',4'-TETRAHYDROXYFLAVONE	DMES906	Investigative	3,7,3',4'-TETRAHYDROXYFLAVONE decreases the expression of Interleukin-4 (IL4).	[36]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid decreases the expression of Interleukin-4 (IL4).	[46]
PATULIN	DM0RV9C	Investigative	PATULIN increases the expression of Interleukin-4 (IL4).	[48]
HONOKIOL	DMJWT3X	Investigative	HONOKIOL decreases the activity of Interleukin-4 (IL4).	[49]
H-89	DM4RVGO	Investigative	H-89 decreases the expression of Interleukin-4 (IL4).	[26]
methyl isocyanate	DME4JGF	Investigative	methyl isocyanate increases the expression of Interleukin-4 (IL4).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the secretion of Interleukin-4 (IL4).	[13]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the secretion of Interleukin-4 (IL4).	[20]
Imiquimod	DM1TMA3	Approved	Imiquimod increases the secretion of Interleukin-4 (IL4).	[27]
Cilomilast	DMHSM7I	Discontinued in Phase 3	Cilomilast decreases the secretion of Interleukin-4 (IL4).	[39]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the secretion of Interleukin-4 (IL4).	[44]
N-nonylphenol	DMH3OUX	Investigative	N-nonylphenol affects the secretion of Interleukin-4 (IL4).	[47]

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