Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBG4SA2)

• DOT Name: Prostaglandin F2 receptor negative regulator (PTGFRN)
• Synonyms: CD9 partner 1; CD9P-1; Glu-Trp-Ile EWI motif-containing protein F; EWI-F; Prostaglandin F2-alpha receptor regulatory protein; Prostaglandin F2-alpha receptor-associated protein; CD antigen CD315
• Gene Name: PTGFRN
• Related Disease:
  Erectile dysfunction
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Prostate carcinoma
  Adult glioblastoma
  Glioblastoma multiforme
• UniProt ID: FPRP_HUMAN
• Pfam ID: PF07686
• Sequence:
  MGRLASRPLLLALLSLALCRGRVVRVPTATLVRVVGTELVIPCNVSDYDGPSEQNFDWSF
  SSLGSSFVELASTWEVGFPAQLYQERLQRGEILLRRTANDAVELHIKNVQPSDQGHYKCS
  TPSTDATVQGNYEDTVQVKVLADSLHVGPSARPPPSLSLREGEPFELRCTAASASPLHTH
  LALLWEVHRGPARRSVLALTHEGRFHPGLGYEQRYHSGDVRLDTVGSDAYRLSVSRALSA
  DQGSYRCIVSEWIAEQGNWQEIQEKAVEVATVVIQPSVLRAAVPKNVSVAEGKELDLTCN
  ITTDRADDVRPEVTWSFSRMPDSTLPGSRVLARLDRDSLVHSSPHVALSHVDARSYHLLV
  RDVSKENSGYYYCHVSLWAPGHNRSWHKVAEAVSSPAGVGVTWLEPDYQVYLNASKVPGF
  ADDPTELACRVVDTKSGEANVRFTVSWYYRMNRRSDNVVTSELLAVMDGDWTLKYGERSK
  QRAQDGDFIFSKEHTDTFNFRIQRTTEEDRGNYYCVVSAWTKQRNNSWVKSKDVFSKPVN
  IFWALEDSVLVVKARQPKPFFAAGNTFEMTCKVSSKNIKSPRYSVLIMAEKPVGDLSSPN
  ETKYIISLDQDSVVKLENWTDASRVDGVVLEKVQEDEFRYRMYQTQVSDAGLYRCMVTAW
  SPVRGSLWREAATSLSNPIEIDFQTSGPIFNASVHSDTPSVIRGDLIKLFCIITVEGAAL
  DPDDMAFDVSWFAVHSFGLDKAPVLLSSLDRKGIVTTSRRDWKSDLSLERVSVLEFLLQV
  HGSEDQDFGNYYCSVTPWVKSPTGSWQKEAEIHSKPVFITVKMDVLNAFKYPLLIGVGLS
  TVIGLLSCLIGYCSSHWCCKKEVQETRRERRRLMSMEMD
• Function: Inhibits the binding of prostaglandin F2-alpha (PGF2-alpha) to its specific FP receptor, by decreasing the receptor number rather than the affinity constant. Functional coupling with the prostaglandin F2-alpha receptor seems to occur. In myoblasts, associates with tetraspanins CD9 and CD81 to prevent myotube fusion during muscle regeneration.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Erectile dysfunction	DISD8MTH	Strong	Genetic Variation	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[2]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Altered Expression	[4]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[5]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[1]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[3]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[3]

14 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 Prostaglandin F2 receptor negative regulator (PTGFRN).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[16]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Prostaglandin F2 receptor negative regulator (PTGFRN).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Prostaglandin F2 receptor negative regulator (PTGFRN).	[18]

References

• [1] Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer.Int J Radiat Oncol Biol Phys. 2010 Dec 1;78(5):1292-300. doi: 10.1016/j.ijrobp.2010.07.036.
• [2] CD9P-1 expression correlates with the metastatic status of lung cancer, and a truncated form of CD9P-1, GS-168AT2, inhibits in vivo tumour growth.Br J Cancer. 2011 Feb 1;104(3):496-504. doi: 10.1038/sj.bjc.6606033. Epub 2011 Jan 4.
• [3] The Ig superfamily protein PTGFRN coordinates survival signaling in glioblastoma multiforme.Cancer Lett. 2019 Oct 10;462:33-42. doi: 10.1016/j.canlet.2019.07.018. Epub 2019 Aug 1.
• [4] Identification of the genomic region under epigenetic regulation during non-alcoholic fatty liver disease progression.Hepatol Res. 2018 Feb;48(3):E320-E334. doi: 10.1111/hepr.12992. Epub 2017 Nov 17.
• [5] Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nat Commun. 2018 Jul 27;9(1):2941. doi: 10.1038/s41467-018-04951-w.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [10] 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.
• [11] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] 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.
• [14] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [15] 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.
• [16] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [17] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [18] 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.
• [19] 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.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.