Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX254AR)

• DOT Name: Secreted phosphoprotein 24 (SPP2)
• Synonyms: Spp-24; Secreted phosphoprotein 2
• Gene Name: SPP2
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Cutaneous melanoma
  Dermatitis
  Endometrial cancer
  Endometrial carcinoma
  Melanoma
  Neoplasm
  Pancreatic cancer
  Hepatocellular carcinoma
  Retinitis pigmentosa
• UniProt ID: SPP24_HUMAN
• Pfam ID: PF07448
• Sequence:
  MISRMEKMTMMMKILIMFALGMNYWSCSGFPVYDYDPSSLRDALSASVVKVNSQSLSPYL
  FRAFRSSLKRVEVLDENNLVMNLEFSIRETTCRKDSGEDPATCAFQRDYYVSTAVCRSTV
  KVSAQQVQGVHARCSWSSSTSESYSSEEMIFGDMLGSHKWRNNYLFGLISDESISEQFYD
  RSLGIMRRVLPPGNRRYPNHRHRARINTDFE
• Function: Could coordinate an aspect of bone turnover.
• Tissue Specificity: Detected in liver and plasma.
• Reactome Pathway:
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Cutaneous melanoma	DIS3MMH9	Strong	Genetic Variation	[1]
Dermatitis	DISY5SZC	Strong	Altered Expression	[2]
Endometrial cancer	DISW0LMR	Strong	Genetic Variation	[1]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[1]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[4]
Retinitis pigmentosa	DISCGPY8	Limited	Autosomal dominant	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Secreted phosphoprotein 24 (SPP2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Secreted phosphoprotein 24 (SPP2).	[9]

5 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 Secreted phosphoprotein 24 (SPP2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Secreted phosphoprotein 24 (SPP2).	[7]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Secreted phosphoprotein 24 (SPP2).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Secreted phosphoprotein 24 (SPP2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Secreted phosphoprotein 24 (SPP2).	[10]

References

• [1] Association between the expression of secreted phosphoprotein - related genes and prognosis of human cancer.BMC Cancer. 2019 Dec 18;19(1):1230. doi: 10.1186/s12885-019-6441-3.
• [2] Sphingosine 1-phosphate phosphatase 2 is induced during inflammatory responses.Cell Signal. 2007 Apr;19(4):748-60. doi: 10.1016/j.cellsig.2006.09.004. Epub 2006 Sep 30.
• [3] Secreted phosphoprotein 24kD (Spp24) inhibits growth of hepatocellular carcinoma in vivo.Environ Toxicol Pharmacol. 2017 Apr;51:51-55. doi: 10.1016/j.etap.2017.03.001. Epub 2017 Mar 4.
• [4] Identification of special key genes for alcohol-related hepatocellular carcinoma through bioinformatic analysis.PeerJ. 2019 Feb 6;7:e6375. doi: 10.7717/peerj.6375. eCollection 2019.
• [5] SPP2 Mutations Cause Autosomal Dominant Retinitis Pigmentosa. Sci Rep. 2015 Oct 13;5:14867. doi: 10.1038/srep14867.
• [6] 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.
• [7] 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.
• [8] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [9] 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.
• [10] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.