Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT81Q8LY)

• DOT Name: Adhesion G protein-coupled receptor L3 (ADGRL3)
• Synonyms: Calcium-independent alpha-latrotoxin receptor 3; CIRL-3; Latrophilin-3; Lectomedin-3
• Gene Name: ADGRL3
• UniProt ID: AGRL3_HUMAN
• PDB ID: 5CMN; 6VHH; 7SF7; 8DJG
• Pfam ID: PF00002 ; PF16489 ; PF02140 ; PF01825 ; PF02793 ; PF02354 ; PF02191
• Sequence:
  MWPSQLLIFMMLLAPIIHAFSRAPIPMAVVRRELSCESYPIELRCPGTDVIMIESANYGR
  TDDKICDSDPAQMENIRCYLPDAYKIMSQRCNNRTQCAVVAGPDVFPDPCPGTYKYLEVQ
  YECVPYKVEQKVFLCPGLLKGVYQSEHLFESDHQSGAWCKDPLQASDKIYYMPWTPYRTD
  TLTEYSSKDDFIAGRPTTTYKLPHRVDGTGFVVYDGALFFNKERTRNIVKFDLRTRIKSG
  EAIIANANYHDTSPYRWGGKSDIDLAVDENGLWVIYATEQNNGKIVISQLNPYTLRIEGT
  WDTAYDKRSASNAFMICGILYVVKSVYEDDDNEATGNKIDYIYNTDQSKDSLVDVPFPNS
  YQYIAAVDYNPRDNLLYVWNNYHVVKYSLDFGPLDSRSGQAHHGQVSYISPPIHLDSELE
  RPSVKDISTTGPLGMGSTTTSTTLRTTTLSPGRSTTPSVSGRRNRSTSTPSPAVEVLDDM
  TTHLPSASSQIPALEESCEAVEAREIMWFKTRQGQIAKQPCPAGTIGVSTYLCLAPDGIW
  DPQGPDLSNCSSPWVNHITQKLKSGETAANIARELAEQTRNHLNAGDITYSVRAMDQLVG
  LLDVQLRNLTPGGKDSAARSLNKAMVETVNNLLQPQALNAWRDLTTSDQLRAATMLLHTV
  EESAFVLADNLLKTDIVRENTDNIKLEVARLSTEGNLEDLKFPENMGHGSTIQLSANTLK
  QNGRNGEIRVAFVLYNNLGPYLSTENASMKLGTEALSTNHSVIVNSPVITAAINKEFSNK
  VYLADPVVFTVKHIKQSEENFNPNCSFWSYSKRTMTGYWSTQGCRLLTTNKTHTTCSCNH
  LTNFAVLMAHVEVKHSDAVHDLLLDVITWVGILLSLVCLLICIFTFCFFRGLQSDRNTIH
  KNLCISLFVAELLFLIGINRTDQPIACAVFAALLHFFFLAAFTWMFLEGVQLYIMLVEVF
  ESEHSRRKYFYLVGYGMPALIVAVSAAVDYRSYGTDKVCWLRLDTYFIWSFIGPATLIIM
  LNVIFLGIALYKMFHHTAILKPESGCLDNIKSWVIGAIALLCLLGLTWAFGLMYINESTV
  IMAYLFTIFNSLQGMFIFIFHCVLQKKVRKEYGKCLRTHCCSGKSTESSIGSGKTSGSRT
  PGRYSTGSQSRIRRMWNDTVRKQSESSFITGDINSSASLNREGLLNNARDTSVMDTLPLN
  GNHGNSYSIASGEYLSNCVQIIDRGYNHNETALEKKILKELTSNYIPSYLNNHERSSEQN
  RNLMNKLVNNLGSGREDDAIVLDDATSFNHEESLGLELIHEESDAPLLPPRVYSTENHQP
  HHYTRRRIPQDHSESFFPLLTNEHTEDLQSPHRDSLYTSMPTLAGVAATESVTTSTQTEP
  PPAKCGDAEDVYYKSMPNLGSRNHVHQLHTYYQLGRGSSDGFIVPPNKDGTPPEGSSKGP
  AHLVTSL
• Function: Plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells. Plays a role in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hexane-1,6-diamine	DMSHF0K	Investigative	Adhesion G protein-coupled receptor L3 (ADGRL3) increases the abundance of Hexane-1,6-diamine.	[11]

11 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 Adhesion G protein-coupled receptor L3 (ADGRL3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[4]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[6]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Adhesion G protein-coupled receptor L3 (ADGRL3).	[9]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Adhesion G protein-coupled receptor L3 (ADGRL3).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Adhesion G protein-coupled receptor L3 (ADGRL3).	[10]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] 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.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [6] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [7] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [8] 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.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [11] DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study. Toxicol Lett. 2014 Dec 1;231(2):217-26. doi: 10.1016/j.toxlet.2014.10.024. Epub 2014 Oct 22.