Details of Drug Off-Target (DOT)

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

• DOT Name: Interleukin-5 (IL5)
• Synonyms: IL-5; B-cell differentiation factor I; Eosinophil differentiation factor; T-cell replacing factor; TRF
• Gene Name: IL5
• UniProt ID: IL5_HUMAN
• PDB ID: 1HUL; 3QT2; 3VA2
• Pfam ID: PF02025
• Sequence:
  MRMLLHLSLLALGAAYVYAIPTEIPTSALVKETLALLSTHRTLLIANETLRIPVPVHKNH
  QLCTEEIFQGIGTLESQTVQGGTVERLFKNLSLIKKYIDGQKKKCGEERRRVNQFLDYLQ
  EFLGVMNTEWIIES
• Function: Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils. Acts also on activated and resting B-cells to induce immunoglobulin production, growth, and differentiation. Mechanistically, exerts its biological effects through a receptor composed of IL5RA subunit and the cytokine receptor common subunit beta/CSF2RB. Binding to the receptor leads to activation of various kinases including LYN, SYK and JAK2 and thereby propagates signals through the RAS-MAPK and JAK-STAT5 pathways respectively.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  IL-17 sig.ling pathway (hsa04657)
  Th1 and Th2 cell differentiation (hsa04658)
  T cell receptor sig.ling pathway (hsa04660)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Intesti.l immune network for IgA production (hsa04672)
  Pathways in cancer (hsa05200)
  Asthma (hsa05310)
  Autoimmune thyroid disease (hsa05320)
  Inflammatory bowel disease (hsa05321)
  Allograft rejection (hsa05330)
• Reactome Pathway:
  RAF/MAP kinase cascade (R-HSA-5673001)
  Interleukin receptor SHC signaling (R-HSA-912526)
  Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetylcholine	DMDF79Z	Approved	Interleukin-5 (IL5) increases the response to substance of Acetylcholine.	[36]
Formoterol	DMSOURV	Approved	Interleukin-5 (IL5) increases the Eosinophilic disorders ADR of Formoterol.	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
LTC4	DM702WR	Investigative	Interleukin-5 (IL5) increases the secretion of LTC4.	[38]

36 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-5 (IL5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Interleukin-5 (IL5).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-5 (IL5).	[3]
Marinol	DM70IK5	Approved	Marinol increases the expression of Interleukin-5 (IL5).	[4]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-5 (IL5).	[5]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the activity of Interleukin-5 (IL5).	[6]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Interleukin-5 (IL5).	[7]
Clozapine	DMFC71L	Approved	Clozapine affects the expression of Interleukin-5 (IL5).	[8]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Interleukin-5 (IL5).	[9]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Interleukin-5 (IL5).	[3]
Lindane	DMB8CNL	Approved	Lindane decreases the expression of Interleukin-5 (IL5).	[10]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Interleukin-5 (IL5).	[11]
Glucosamine	DM4ZLFD	Approved	Glucosamine decreases the expression of Interleukin-5 (IL5).	[14]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the expression of Interleukin-5 (IL5).	[15]
Prednisone	DM2HG4X	Approved	Prednisone decreases the expression of Interleukin-5 (IL5).	[17]
Terbinafine	DMI6HUW	Approved	Terbinafine decreases the expression of Interleukin-5 (IL5).	[18]
Miconazole	DMPMYE8	Approved	Miconazole decreases the expression of Interleukin-5 (IL5).	[18]
Fluticasone propionate	DMRWLB2	Approved	Fluticasone propionate decreases the expression of Interleukin-5 (IL5).	[19]
Itraconazole	DMCR1MV	Approved	Itraconazole decreases the expression of Interleukin-5 (IL5).	[18]
Betamethasone valerate	DMMIAXO	Approved	Betamethasone valerate decreases the expression of Interleukin-5 (IL5).	[20]
Pranlukast	DMYHDCA	Approved	Pranlukast decreases the expression of Interleukin-5 (IL5).	[21]
Epinastine	DMX0K3Q	Approved	Epinastine decreases the expression of Interleukin-5 (IL5).	[22]
Tolnaftate	DM28MU7	Approved	Tolnaftate decreases the expression of Interleukin-5 (IL5).	[18]
Praziquantel	DMOU1PK	Approved	Praziquantel increases the expression of Interleukin-5 (IL5).	[23]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate decreases the expression of Interleukin-5 (IL5).	[24]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Interleukin-5 (IL5).	[25]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Interleukin-5 (IL5).	[26]
Ribavirin	DMEYLH9	Phase 1 Trial	Ribavirin decreases the expression of Interleukin-5 (IL5).	[27]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Interleukin-5 (IL5).	[28]
Terfenadine	DM4KLPT	Withdrawn from market	Terfenadine decreases the expression of Interleukin-5 (IL5).	[29]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid decreases the expression of Interleukin-5 (IL5).	[34]
Staurosporine	DM0E9BR	Investigative	Staurosporine decreases the activity of Interleukin-5 (IL5).	[35]
H-89	DM4RVGO	Investigative	H-89 decreases the expression of Interleukin-5 (IL5).	[18]
Bisindolylmaleimide-I	DMOQJZC	Investigative	Bisindolylmaleimide-I decreases the activity of Interleukin-5 (IL5).	[35]
Clobenpropit	DM537OH	Investigative	Clobenpropit affects the expression of Interleukin-5 (IL5).	[8]
Dimaprit	DMA4NI2	Investigative	Dimaprit affects the expression of Interleukin-5 (IL5).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the secretion of Interleukin-5 (IL5).	[12]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide decreases the secretion of Interleukin-5 (IL5).	[13]
Pomalidomide	DMTGBAX	Approved	Pomalidomide decreases the secretion of Interleukin-5 (IL5).	[16]
Cilomilast	DMHSM7I	Discontinued in Phase 3	Cilomilast decreases the secretion of Interleukin-5 (IL5).	[30]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the secretion of Interleukin-5 (IL5).	[32]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the secretion of Interleukin-5 (IL5).	[33]
Nitrosoglutathione	DMZ9WI4	Investigative	Nitrosoglutathione decreases the secretion of Interleukin-5 (IL5).	[13]

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 Interleukin-5 (IL5).	[31]

References

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