Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4TRT4K)

• DOT Name: PRELI domain containing protein 3B (PRELID3B)
• Synonyms: Protein slowmo homolog 2
• Gene Name: PRELID3B
• UniProt ID: PLD3B_HUMAN
• PDB ID: 6I4Y
• Pfam ID: PF04707
• Sequence:
  MKIWTSEHVFDHPWETVTTAAMQKYPNPMNPSVVGVDVLDRHIDPSGKLHSHRLLSTEWG
  LPSIVKSLIGAARTKTYVQEHSVVDPVEKTMELKSTNISFTNMVSVDERLIYKPHPQDPE
  KTVLTQEAIITVKGVSLSSYLEGLMASTISSNASKGREAMEWVIHKLNAEIEELTASARG
  TIRTPMAAAAFAEK

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	PRELI domain containing protein 3B (PRELID3B) affects the response to substance of Methotrexate.	[11]
Mitoxantrone	DMM39BF	Approved	PRELI domain containing protein 3B (PRELID3B) affects the response to substance of Mitoxantrone.	[11]

8 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 PRELI domain containing protein 3B (PRELID3B).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PRELI domain containing protein 3B (PRELID3B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PRELI domain containing protein 3B (PRELID3B).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of PRELI domain containing protein 3B (PRELID3B).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of PRELI domain containing protein 3B (PRELID3B).	[5]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of PRELI domain containing protein 3B (PRELID3B).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of PRELI domain containing protein 3B (PRELID3B).	[9]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of PRELI domain containing protein 3B (PRELID3B).	[10]

2 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 affects the methylation of PRELI domain containing protein 3B (PRELID3B).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of PRELI domain containing protein 3B (PRELID3B).	[7]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] 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] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 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] 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.
• [8] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [11] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.