Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB2HQ4S)

• DOT Name: Phospholipid phosphatase-related protein type 2 (PLPPR2)
• Synonyms: Inactive phospholipid phosphatase PLPPR2; Lipid phosphate phosphatase-related protein type 2; Plasticity-related gene 4 protein; PRG-4
• Gene Name: PLPPR2
• UniProt ID: PLPR2_HUMAN
• Pfam ID: PF01569
• Sequence:
  MAGGRPHLKRSFSIIPCFVFVESVLLGIVILLAYRLEFTDTFPVHTQGFFCYDSTYAKPY
  PGPEAASRVPPALVYALVTAGPTLTILLGELARAFFPAPPSAVPVIGESTIVSGACCRFS
  PPVRRLVRFLGVYSFGLFTTTIFANAGQVVTGNPTPHFLSVCRPNYTALGCLPPSPDRPG
  PDRFVTDQGACAGSPSLVAAARRAFPCKDAALCAYAVTYTAMYVTLVFRVKGSRLVKPSL
  CLALLCPAFLVGVVRVAEYRNHWSDVLAGFLTGAAIATFLVTCVVHNFQSRPPSGRRLSP
  WEDLGQAPTMDSPLEKNPRSAGRIRHRHGSPHPSRRTAPAVAT
• Reactome Pathway: Lysosphingolipid and LPA receptors (R-HSA-419408)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[4]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Phospholipid phosphatase-related protein type 2 (PLPPR2).	[8]

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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [6] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.