Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPM9N4T)

• DOT Name: Sprouty-related, EVH1 domain-containing protein 3 (SPRED3)
• Synonyms: Spred-3
• Gene Name: SPRED3
• UniProt ID: SPRE3_HUMAN
• Pfam ID: PF05210 ; PF00568
• Sequence:
  MVRVRAVVMARDDSSGGWLPVGGGGLSQVSVCRVRGARPEGGARQGHYVIHGERLRDQKT
  TLECTLKPGLVYNKVNPIFHHWSLGDCKFGLTFQSPAEADEFQKSLLAALAALGRGSLTP
  SSSSSSSSPSQDTAETPCPLTSHVDSDSSSSHSRQETPPSAAAAPIITMESASGFGPTTP
  PQRRRSSAQSYPPLLPFTGIPEPSEPLAGAGGLGWGGRGYEDYRRSGPPAPLALSTCVVR
  FAKTGALRGAALGPPAALPAPLTEAAPPAPPARPPPGPGPSSAPAKASPEAEEAARCVHC
  RALFRRRADGRGGRCAEAPDPGRLLVRRLSCLWCAESLLYHCLSDAEGDFSDPCACEPGH
  PRPAARWAALAALSLAVPCLCCYAPLRACHWVAARCGCAGCGGRHEEAAR
• Function: Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase. Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2. Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells.
• Reactome Pathway:
  RAS signaling downstream of NF1 loss-of-function variants (R-HSA-6802953)
  Regulation of RAS by GAPs (R-HSA-5658442)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Sprouty-related, EVH1 domain-containing protein 3 (SPRED3).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sprouty-related, EVH1 domain-containing protein 3 (SPRED3).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sprouty-related, EVH1 domain-containing protein 3 (SPRED3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Sprouty-related, EVH1 domain-containing protein 3 (SPRED3).	[4]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Sprouty-related, EVH1 domain-containing protein 3 (SPRED3).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sprouty-related, EVH1 domain-containing protein 3 (SPRED3).	[7]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Sprouty-related, EVH1 domain-containing protein 3 (SPRED3).	[8]

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 Sprouty-related, EVH1 domain-containing protein 3 (SPRED3).	[6]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.