Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY5G543)

• DOT Name: Prostamide/prostaglandin F synthase (PRXL2B)
• Synonyms: Prostamide/PG F synthase; Prostamide/PGF synthase; EC 1.11.1.20; Peroxiredoxin-like 2B; Protein FAM213B
• Gene Name: PRXL2B
• UniProt ID: PXL2B_HUMAN
• EC Number: 1.11.1.20
• Pfam ID: PF13911
• Sequence:
  MSTVDLARVGACILKHAVTGEAVELRSLWREHACVVAGLRRFGCVVCRWIAQDLSSLAGL
  LDQHGVRLVGVGPEALGLQEFLDGDYFAGELYLDESKQLYKELGFKRYNSLSILPAALGK
  PVRDVAAKAKAVGIQGNLSGDLLQSGGLLVVSKGGDKVLLHFVQKSPGDYVPKEHILQVL
  GISAEVCASDPPQCDREV
• Function: Catalyzes the reduction of prostaglandin-ethanolamide H(2) (prostamide H(2)) to prostamide F(2alpha) with NADPH as proton donor. Also able to reduce prostaglandin H(2) to prostaglandin F(2alpha).
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123)

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 Prostamide/prostaglandin F synthase (PRXL2B).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Prostamide/prostaglandin F synthase (PRXL2B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prostamide/prostaglandin F synthase (PRXL2B).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Prostamide/prostaglandin F synthase (PRXL2B).	[4]
Marinol	DM70IK5	Approved	Marinol increases the expression of Prostamide/prostaglandin F synthase (PRXL2B).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Prostamide/prostaglandin F synthase (PRXL2B).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Prostamide/prostaglandin F synthase (PRXL2B).	[7]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Prostamide/prostaglandin F synthase (PRXL2B).	[8]
Lindane	DMB8CNL	Approved	Lindane decreases the expression of Prostamide/prostaglandin F synthase (PRXL2B).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Prostamide/prostaglandin F synthase (PRXL2B).	[9]

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] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [5] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [8] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [9] 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.