Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT018P93)

• DOT Name: SLIT and NTRK-like protein 3 (SLITRK3)
• Gene Name: SLITRK3
• Related Disease:
  Neoplasm
  Gastrointestinal stromal tumour
• UniProt ID: SLIK3_HUMAN
• Pfam ID: PF13855
• Sequence:
  MKPSIAEMLHRGRMLWIILLSTIALGWTTPIPLIEDSEEIDEPCFDPCYCEVKESLFHIH
  CDSKGFTNISQITEFWSRPFKLYLQRNSMRKLYTNSFLHLNNAVSINLGNNALQDIQTGA
  FNGLKILKRLYLHENKLDVFRNDTFLGLESLEYLQADYNVIKRIESGAFRNLSKLRVLIL
  NDNLIPMLPTNLFKAVSLTHLDLRGNRLKVLFYRGMLDHIGRSLMELQLEENPWNCTCEI
  VQLKSWLERIPYTALVGDITCETPFHFHGKDLREIRKTELCPLLSDSEVEASLGIPHSSS
  SKENAWPTKPSSMLSSVHFTASSVEYKSSNKQPKPTKQPRTPRPPSTSQALYPGPNQPPI
  APYQTRPPIPIICPTGCTCNLHINDLGLTVNCKERGFNNISELLPRPLNAKKLYLSSNLI
  QKIYRSDFWNFSSLDLLHLGNNRISYVQDGAFINLPNLKSLFLNGNDIEKLTPGMFRGLQ
  SLHYLYFEFNVIREIQPAAFSLMPNLKLLFLNNNLLRTLPTDAFAGTSLARLNLRKNYFL
  YLPVAGVLEHLNAIVQIDLNENPWDCTCDLVPFKQWIETISSVSVVGDVLCRSPENLTHR
  DVRTIELEVLCPEMLHVAPAGESPAQPGDSHLIGAPTSASPYEFSPPGGPVPLSVLILSL
  LVLFFSAVFVAAGLFAYVLRRRRKKLPFRSKRQEGVDLTGIQMQCHRLFEDGGGGGGGSG
  GGGRPTLSSPEKAPPVGHVYEYIPHPVTQMCNNPIYKPREEEEVAVSSAQEAGSAERGGP
  GTQPPGMGEALLGSEQFAETPKENHSNYRTLLEKEKEWALAVSSSQLNTIVTVNHHHPHH
  PAVGGVSGVVGGTGGDLAGFRHHEKNGGVVLFPPGGGCGSGSMLLDRERPQPAPCTVGFV
  DCLYGTVPKLKELHVHPPGMQYPDLQQDARLKETLLFSAGKGFTDHQTQKSDYLELRAKL
  QTKPDYLEVLEKTTYRF
• Function: Suppresses neurite outgrowth.
• Tissue Specificity: Expressed in the occipital lobe of the cerebral cortex of the brain. Expressed at higher levels in some astrocytic brain tumors such as astrocytomas, oligodendrogliomas, glioblastomas, gangliogliomas and primitive neuroectodermal tumors.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway:
  RAC3 GTPase cycle (R-HSA-9013423)
  Receptor-type tyrosine-protein phosphatases (R-HSA-388844)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Altered Expression	[1]

6 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 SLIT and NTRK-like protein 3 (SLITRK3).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of SLIT and NTRK-like protein 3 (SLITRK3).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of SLIT and NTRK-like protein 3 (SLITRK3).	[3]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of SLIT and NTRK-like protein 3 (SLITRK3).	[4]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of SLIT and NTRK-like protein 3 (SLITRK3).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of SLIT and NTRK-like protein 3 (SLITRK3).	[7]

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 SLIT and NTRK-like protein 3 (SLITRK3).	[6]

References

• [1] SLITRK3 expression correlation to gastrointestinal stromal tumor risk rating and prognosis.World J Gastroenterol. 2015 Jul 21;21(27):8398-407. doi: 10.3748/wjg.v21.i27.8398.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [5] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [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.