Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSCN5AM)

• DOT Name: SLIT and NTRK-like protein 4 (SLITRK4)
• Gene Name: SLITRK4
• UniProt ID: SLIK4_HUMAN
• Pfam ID: PF13855
• Sequence:
  MFLWLFLILSALISSTNADSDISVEICNVCSCVSVENVLYVNCEKVSVYRPNQLKPPWSN
  FYHLNFQNNFLNILYPNTFLNFSHAVSLHLGNNKLQNIEGGAFLGLSALKQLHLNNNELK
  ILRADTFLGIENLEYLQADYNLIKYIERGAFNKLHKLKVLILNDNLISFLPDNIFRFASL
  THLDIRGNRIQKLPYIGVLEHIGRVVELQLEDNPWNCSCDLLPLKAWLENMPYNIYIGEA
  ICETPSDLYGRLLKETNKQELCPMGTGSDFDVRILPPSQLENGYTTPNGHTTQTSLHRLV
  TKPPKTTNPSKISGIVAGKALSNRNLSQIVSYQTRVPPLTPCPAPCFCKTHPSDLGLSVN
  CQEKNIQSMSELIPKPLNAKKLHVNGNSIKDVDVSDFTDFEGLDLLHLGSNQITVIKGDV
  FHNLTNLRRLYLNGNQIERLYPEIFSGLHNLQYLYLEYNLIKEISAGTFDSMPNLQLLYL
  NNNLLKSLPVYIFSGAPLARLNLRNNKFMYLPVSGVLDQLQSLTQIDLEGNPWDCTCDLV
  ALKLWVEKLSDGIVVKELKCETPVQFANIELKSLKNEILCPKLLNKPSAPFTSPAPAITF
  TTPLGPIRSPPGGPVPLSILILSILVVLILTVFVAFCLLVFVLRRNKKPTVKHEGLGNPD
  CGSMQLQLRKHDHKTNKKDGLSTEAFIPQTIEQMSKSHTCGLKESETGFMFSDPPGQKVV
  MRNVADKEKDLLHVDTRKRLSTIDELDELFPSRDSNVFIQNFLESKKEYNSIGVSGFEIR
  YPEKQPDKKSKKSLIGGNHSKIVVEQRKSEYFELKAKLQSSPDYLQVLEEQTALNKI
• Function: It is involved in synaptogenesis and promotes synapse differentiation. Suppresses neurite outgrowth.
• Tissue Specificity: Expressed in the cerebral cortex of the brain and at higher levels in some astrocytic brain tumors such as astrocytomas, glioblastomas and primitive neuroectodermal tumors.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway: Receptor-type tyrosine-protein phosphatases (R-HSA-388844)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[10]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[12]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of SLIT and NTRK-like protein 4 (SLITRK4).	[13]

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 4 (SLITRK4).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] 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.
• [10] 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.
• [11] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.