Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDC3Y8O)

• DOT Name: Interleukin-3 receptor subunit alpha (IL3RA)
• Synonyms: IL-3 receptor subunit alpha; IL-3R subunit alpha; IL-3R-alpha; IL-3RA; CD antigen CD123
• Gene Name: IL3RA
• UniProt ID: IL3RA_HUMAN
• PDB ID: 4JZJ; 5UV8; 5UWC; 6NMY
• Pfam ID: PF18611 ; PF09240
• Sequence:
  MVLLWLTLLLIALPCLLQTKEDPNPPITNLRMKAKAQQLTWDLNRNVTDIECVKDADYSM
  PAVNNSYCQFGAISLCEVTNYTVRVANPPFSTWILFPENSGKPWAGAENLTCWIHDVDFL
  SCSWAVGPGAPADVQYDLYLNVANRRQQYECLHYKTDAQGTRIGCRFDDISRLSSGSQSS
  HILVRGRSAAFGIPCTDKFVVFSQIEILTPPNMTAKCNKTHSFMHWKMRSHFNRKFRYEL
  QIQKRMQPVITEQVRDRTSFQLLNPGTYTVQIRARERVYEFLSAWSTPQRFECDQEEGAN
  TRAWRTSLLIALGTLLALVCVFVICRRYLVMQRLFPRIPHMKDPIGDSFQNDKLVVWEAG
  KAGLEECLVTEVQVVQKT
• Function: Cell surface receptor for IL3 expressed on hematopoietic progenitor cells, monocytes and B-lymphocytes that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells. Ligand stimulation rapidly induces hetrodimerization with IL3RB, phosphorylation and enzyme activity of effector proteins such as JAK2 and PI3K that play a role in signaling cell proliferation and differentiation. Activation of JAK2 leads to STAT5-mediated transcriptional program.
• 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)
  Pathways in cancer (hsa05200)
• 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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Interleukin-3 receptor subunit alpha (IL3RA).	[1]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Interleukin-3 receptor subunit alpha (IL3RA).	[2]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Interleukin-3 receptor subunit alpha (IL3RA).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Interleukin-3 receptor subunit alpha (IL3RA).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Interleukin-3 receptor subunit alpha (IL3RA).	[3]
Tacedinaline	DM1Z74X	Discontinued in Phase 2	Tacedinaline increases the expression of Interleukin-3 receptor subunit alpha (IL3RA).	[2]

References

• [1] The effect to IL-3Ralpha, downstream PI3k/Akt signaling of all-trans retinoic acid and arsenic trioxide in NB4 cells. Pharmazie. 2014 Apr;69(4):297-300.
• [2] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [3] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.