Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWZH98J)

• DOT Name: Pigment epithelium-derived factor (SERPINF1)
• Synonyms: PEDF; Cell proliferation-inducing gene 35 protein; EPC-1; Serpin F1
• Gene Name: SERPINF1
• Related Disease:
  Osteogenesis imperfecta type 6
  Osteogenesis imperfecta type 3
  Osteogenesis imperfecta type 4
• UniProt ID: PEDF_HUMAN
• PDB ID: 1IMV
• Pfam ID: PF00079
• Sequence:
  MQALVLLLCIGALLGHSSCQNPASPPEEGSPDPDSTGALVEEEDPFFKVPVNKLAAAVSN
  FGYDLYRVRSSTSPTTNVLLSPLSVATALSALSLGAEQRTESIIHRALYYDLISSPDIHG
  TYKELLDTVTAPQKNLKSASRIVFEKKLRIKSSFVAPLEKSYGTRPRVLTGNPRLDLQEI
  NNWVQAQMKGKLARSTKEIPDEISILLLGVAHFKGQWVTKFDSRKTSLEDFYLDEERTVR
  VPMMSDPKAVLRYGLDSDLSCKIAQLPLTGSMSIIFFLPLKVTQNLTLIEESLTSEFIHD
  IDRELKTVQAVLTVPKLKLSYEGEVTKSLQEMKLQSLFDSPDFSKITGKPIKLTQVEHRA
  GFEWNEDGAGTTPSPGLQPAHLTFPLDYHLNQPFIFVLRDTDTGALLFIGKILDPRGP
• Function: Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells. Potent inhibitor of angiogenesis. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity.
• Tissue Specificity: Retinal pigment epithelial cells and blood plasma.
• KEGG Pathway: Wnt sig.ling pathway (hsa04310)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteogenesis imperfecta type 6	DIS0ZNUU	Strong	Autosomal recessive	[1]
Osteogenesis imperfecta type 3	DISFJVSJ	Supportive	Autosomal dominant	[2]
Osteogenesis imperfecta type 4	DIS8S46L	Supportive	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pigment epithelium-derived factor (SERPINF1).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Pigment epithelium-derived factor (SERPINF1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of Pigment epithelium-derived factor (SERPINF1).	[15]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Pigment epithelium-derived factor (SERPINF1).	[16]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[17]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[18]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[18]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Pigment epithelium-derived factor (SERPINF1).	[19]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[20]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[21]
Propofol	DMB4OLE	Approved	Propofol increases the expression of Pigment epithelium-derived factor (SERPINF1).	[22]
Sevoflurane	DMC9O43	Approved	Sevoflurane decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[22]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Pigment epithelium-derived factor (SERPINF1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Pigment epithelium-derived factor (SERPINF1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pigment epithelium-derived factor (SERPINF1).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Pigment epithelium-derived factor (SERPINF1).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Pigment epithelium-derived factor (SERPINF1).	[29]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the secretion of Pigment epithelium-derived factor (SERPINF1).	[23]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the secretion of Pigment epithelium-derived factor (SERPINF1).	[23]

References

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• [11] Role of pigment epithelium-derived factor (PEDF) on arsenic-induced neuronal apoptosis. Chemosphere. 2019 Jan;215:925-931. doi: 10.1016/j.chemosphere.2018.10.100. Epub 2018 Oct 16.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
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• [16] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
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• [20] Nornicotine and Nicotine Induced Neovascularization via Increased VEGF/PEDF Ratio. Ophthalmic Res. 2015;55(1):1-9. doi: 10.1159/000440847. Epub 2015 Nov 5.
• [21] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
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