Details of Drug Off-Target (DOT)

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

• DOT Name: Inactive phospholipase D5 (PLD5)
• Synonyms: Inactive PLD 5; Inactive choline phosphatase 5; Inactive phosphatidylcholine-hydrolyzing phospholipase D5; PLDc
• Gene Name: PLD5
• Related Disease:
  Neoplasm
  Autism
  Leiomyoma
  Uterine fibroids
• UniProt ID: PLD5_HUMAN
• Pfam ID: PF13918
• Sequence:
  MEIRQHEWLSASPHEGFEQMRLKSRPKEPSPSLTRVGANFYSSVKQQDYSASVWLRRKDK
  LEHSQQKCIVIFALVCCFAILVALIFSAVDIMGEDEDGLSEKNCQNKCRIALVENIPEGL
  NYSENAPFHLSLFQGWMNLLNMAKKSVDIVSSHWDLNHTHPSACQGQRLFEKLLQLTSQN
  IEIKLVSDVTADSKVLEALKLKGAEVTYMNMTAYNKGRLQSSFWIVDKQHVYIGSAGLDW
  QSLGQMKELGVIFYNCSCLVLDLQRIFALYSSLKFKSRVPQTWSKRLYGVYDNEKKLQLQ
  LNETKSQAFVSNSPKLFCPKNRSFDIDAIYSVIDDAKQYVYIAVMDYLPISSTSTKRTYW
  PDLDAKIREALVLRSVRVRLLLSFWKETDPLTFNFISSLKAICTEIANCSLKVKFFDLER
  ENACATKEQKNHTFPRLNRNKYMVTDGAAYIGNFDWVGNDFTQNAGTGLVINQADVRNNR
  SIIKQLKDVFERDWYSPYAKTLQPTKQPNCSSLFKLKPLSNKTATDDTGGKDPRNV

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Autism	DISV4V1Z	Strong	Biomarker	[2]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[3]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[3]

15 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 Inactive phospholipase D5 (PLD5).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Inactive phospholipase D5 (PLD5).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Inactive phospholipase D5 (PLD5).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Inactive phospholipase D5 (PLD5).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Inactive phospholipase D5 (PLD5).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Inactive phospholipase D5 (PLD5).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Inactive phospholipase D5 (PLD5).	[10]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Inactive phospholipase D5 (PLD5).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Inactive phospholipase D5 (PLD5).	[12]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Inactive phospholipase D5 (PLD5).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Inactive phospholipase D5 (PLD5).	[14]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Inactive phospholipase D5 (PLD5).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Inactive phospholipase D5 (PLD5).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Inactive phospholipase D5 (PLD5).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Inactive phospholipase D5 (PLD5).	[17]

References

• [1] Multiple hits for the association of uterine fibroids on human chromosome 1q43.PLoS One. 2013;8(3):e58399. doi: 10.1371/journal.pone.0058399. Epub 2013 Mar 14.
• [2] A genome-wide scan for common alleles affecting risk for autism.Hum Mol Genet. 2010 Oct 15;19(20):4072-82. doi: 10.1093/hmg/ddq307. Epub 2010 Jul 27.
• [3] Fine mapping of the uterine leiomyoma locus on 1q43 close to a lncRNA in the RGS7-FH interval.Endocr Relat Cancer. 2015 Aug;22(4):633-43. doi: 10.1530/ERC-15-0208. Epub 2015 Jun 25.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [10] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [14] 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.
• [15] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [16] 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.
• [17] 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.