Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0CQ35N)

• DOT Name: Interleukin-3 (IL3)
• Synonyms: IL-3; Hematopoietic growth factor; Mast cell growth factor; MCGF; Multipotential colony-stimulating factor; P-cell-stimulating factor
• Gene Name: IL3
• Related Disease:
  Childhood acute lymphoblastic leukemia
  Melanoma
  Type-1 diabetes
  Type-1/2 diabetes
  Acute lymphocytic leukaemia
  Acute megakaryoblastic leukemia
  Allergic asthma
  Autoimmune disease
  Bladder cancer
  Breast cancer
  Chronic myelomonocytic leukemia
  Classic Hodgkin lymphoma
  Cutaneous mastocytosis
  Diamond-Blackfan anemia
  Esophageal squamous cell carcinoma
  Fanconi anemia complementation group A
  Fanconi's anemia
  Graves disease
  Immunodeficiency
  leukaemia
  Malignant mesothelioma
  Myeloproliferative neoplasm
  Non-alcoholic fatty liver disease
  Non-alcoholic steatohepatitis
  Non-insulin dependent diabetes
  Osteoarthritis
  Osteosarcoma
  Plasma cell myeloma
  Promyelocytic leukaemia
  Schizophrenia
  Small lymphocytic lymphoma
  Thrombocytopenia
  Advanced cancer
  Anemia
  Myelodysplastic syndrome
  Myeloid leukaemia
  Neuroblastoma
  Polycythemia vera
  Pyelonephritis
  Childhood myelodysplastic syndrome
  Acute leukaemia
  Arthritis
  Blastic plasmacytoid dendritic cell neoplasm
  Breast carcinoma
  Chromosomal disorder
  Leukemia
  Leukopenia
• UniProt ID: IL3_HUMAN
• PDB ID: 1JLI; 5UV8; 5UWC; 6NMY
• Pfam ID: PF02059
• Sequence:
  MSRLPVLLLLQLLVRPGLQAPMTQTTPLKTSWVNCSNMIDEIITHLKQPPLPLLDFNNLN
  GEDQDILMENNLRRPNLEAFNRAVKSLQNASAIESILKNLLPCLPLATAAPTRHPIHIKD
  GDWNEFRRKLTFYLKTLENAQAQQTTLSLAIF
• Function: Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells. Stimulates also mature basophils, eosinophils, and monocytes to become functionally activated. In addition, plays an important role in neural cell proliferation and survival. Participates as well in bone homeostasis and inhibits osteoclast differentiation by preventing NF-kappa-B nuclear translocation and activation. Mechanistically, exerts its biological effects through a receptor composed of IL3RA subunit and a signal transducing subunit IL3RB. Receptor stimulation results in the rapid activation of JAK2 kinase activity leading to STAT5-mediated transcriptional program. Alternatively, contributes to cell survival under oxidative stress in non-hematopoietic systems by activating pathways mediated by PI3K/AKT and ERK.
• Tissue Specificity: Activated T-cells, mast cells, natural killer cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt sig.ling pathway (hsa04151)
  Apoptosis (hsa04210)
  JAK-STAT sig.ling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Acute myeloid leukemia (hsa05221)
  Asthma (hsa05310)
• Reactome Pathway:
  RAF/MAP kinase cascade (R-HSA-5673001)
  RUNX1 regulates transcription of genes involved in interleukin signaling (R-HSA-8939247)
  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

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Childhood acute lymphoblastic leukemia	DISJ5D6U	Definitive	Genetic Variation	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Type-1 diabetes	DIS7HLUB	Definitive	Altered Expression	[3]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[3]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[4]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[5]
Allergic asthma	DISHF0H3	Strong	Biomarker	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Bladder cancer	DISUHNM0	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[9]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Biomarker	[10]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[11]
Cutaneous mastocytosis	DISLBZEF	Strong	Genetic Variation	[12]
Diamond-Blackfan anemia	DISI2SNW	Strong	Altered Expression	[13]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[14]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[15]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[15]
Graves disease	DISU4KOQ	Strong	Genetic Variation	[16]
Immunodeficiency	DIS093I0	Strong	Biomarker	[17]
leukaemia	DISS7D1V	Strong	Biomarker	[18]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[19]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Biomarker	[20]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[21]
Non-alcoholic steatohepatitis	DIST4788	Strong	Biomarker	[21]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[3]
Osteoarthritis	DIS05URM	Strong	Biomarker	[22]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[23]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[24]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[25]
Schizophrenia	DISSRV2N	Strong	Biomarker	[26]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[27]
Thrombocytopenia	DISU61YW	Strong	Therapeutic	[28]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[29]
Anemia	DISTVL0C	moderate	Therapeutic	[30]
Myelodysplastic syndrome	DISYHNUI	moderate	Altered Expression	[31]
Myeloid leukaemia	DISMN944	moderate	Biomarker	[32]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[33]
Polycythemia vera	DISB5FPO	moderate	Biomarker	[34]
Pyelonephritis	DISAOX93	moderate	Biomarker	[35]
Childhood myelodysplastic syndrome	DISMN80I	Disputed	Altered Expression	[31]
Acute leukaemia	DISDQFDI	Limited	Biomarker	[36]
Arthritis	DIST1YEL	Limited	Biomarker	[37]
Blastic plasmacytoid dendritic cell neoplasm	DISLEJU7	Limited	Biomarker	[38]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[9]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[39]
Leukemia	DISNAKFL	Limited	Altered Expression	[40]
Leukopenia	DISJMBMM	Limited	Biomarker	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cytarabine	DMZD5QR	Approved	Interleukin-3 (IL3) increases the Cell-mediated cytotoxicity ADR of Cytarabine.	[53]
Zidovudine	DM4KI7O	Approved	Interleukin-3 (IL3) increases the Hematopoiesis impaired ADR of Zidovudine.	[53]
Famotidine	DMRL3AB	Approved	Interleukin-3 (IL3) increases the Bone marrow failure ADR of Famotidine.	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interleukin-3 (IL3).	[42]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interleukin-3 (IL3).	[43]
Marinol	DM70IK5	Approved	Marinol increases the expression of Interleukin-3 (IL3).	[44]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-3 (IL3).	[45]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Interleukin-3 (IL3).	[44]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Interleukin-3 (IL3).	[46]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the expression of Interleukin-3 (IL3).	[47]
Betamethasone valerate	DMMIAXO	Approved	Betamethasone valerate decreases the expression of Interleukin-3 (IL3).	[47]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Interleukin-3 (IL3).	[48]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-3 (IL3).	[50]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Interleukin-3 (IL3).	[45]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Interleukin-3 (IL3).	[51]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Interleukin-3 (IL3).	[52]

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-3 (IL3).	[49]

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