Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJF68M6)

• DOT Name: Inactive pancreatic lipase-related protein 1 (PNLIPRP1)
• Synonyms: PL-RP1
• Gene Name: PNLIPRP1
• UniProt ID: LIPR1_HUMAN
• PDB ID: 2PPL
• Pfam ID: PF00151 ; PF01477
• Sequence:
  MLIFWTITLFLLGAAKGKEVCYEDLGCFSDTEPWGGTAIRPLKILPWSPEKIGTRFLLYT
  NENPNNFQILLLSDPSTIEASNFQMDRKTRFIIHGFIDKGDESWVTDMCKKLFEVEEVNC
  ICVDWKKGSQATYTQAANNVRVVGAQVAQMLDILLTEYSYPPSKVHLIGHSLGAHVAGEA
  GSKTPGLSRITGLDPVEASFESTPEEVRLDPSDADFVDVIHTDAAPLIPFLGFGTNQQMG
  HLDFFPNGGESMPGCKKNALSQIVDLDGIWAGTRDFVACNHLRSYKYYLESILNPDGFAA
  YPCTSYKSFESDKCFPCPDQGCPQMGHYADKFAGRTSEEQQKFFLNTGEASNFARWRYGV
  SITLSGRTATGQIKVALFGNKGNTHQYSIFRGILKPGSTHSYEFDAKLDVGTIEKVKFLW
  NNNVINPTLPKVGATKITVQKGEEKTVYNFCSEDTVREDTLLTLTPC
• Function: May function as inhibitor of dietary triglyceride digestion. Lacks detectable lipase activity towards triglycerides, diglycerides, phosphatidylcholine, galactolipids or cholesterol esters (in vitro).
• Tissue Specificity: Pancreas.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Metabolic pathways (hsa01100)
  Pancreatic secretion (hsa04972)
  Fat digestion and absorption (hsa04975)
• Reactome Pathway: Digestion of dietary lipid (R-HSA-192456)

Molecular Interaction Atlas (MIA) of This DOT

2 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 Inactive pancreatic lipase-related protein 1 (PNLIPRP1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Inactive pancreatic lipase-related protein 1 (PNLIPRP1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of Inactive pancreatic lipase-related protein 1 (PNLIPRP1).	[2]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Inactive pancreatic lipase-related protein 1 (PNLIPRP1).	[3]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Inactive pancreatic lipase-related protein 1 (PNLIPRP1).	[4]

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] Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
• [3] 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.
• [4] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [5] 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.