Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWP62UA)

• DOT Name: Periostin (POSTN)
• Synonyms: PN; Osteoblast-specific factor 2; OSF-2
• Gene Name: POSTN
• UniProt ID: POSTN_HUMAN
• PDB ID: 5WT7; 5YJG; 5YJH
• Pfam ID: PF02469
• Sequence:
  MIPFLPMFSLLLLLIVNPINANNHYDKILAHSRIRGRDQGPNVCALQQILGTKKKYFSTC
  KNWYKKSICGQKTTVLYECCPGYMRMEGMKGCPAVLPIDHVYGTLGIVGATTTQRYSDAS
  KLREEIEGKGSFTYFAPSNEAWDNLDSDIRRGLESNVNVELLNALHSHMINKRMLTKDLK
  NGMIIPSMYNNLGLFINHYPNGVVTVNCARIIHGNQIATNGVVHVIDRVLTQIGTSIQDF
  IEAEDDLSSFRAAAITSDILEALGRDGHFTLFAPTNEAFEKLPRGVLERIMGDKVASEAL
  MKYHILNTLQCSESIMGGAVFETLEGNTIEIGCDGDSITVNGIKMVNKKDIVTNNGVIHL
  IDQVLIPDSAKQVIELAGKQQTTFTDLVAQLGLASALRPDGEYTLLAPVNNAFSDDTLSM
  DQRLLKLILQNHILKVKVGLNELYNGQILETIGGKQLRVFVYRTAVCIENSCMEKGSKQG
  RNGAIHIFREIIKPAEKSLHEKLKQDKRFSTFLSLLEAADLKELLTQPGDWTLFVPTNDA
  FKGMTSEEKEILIRDKNALQNIILYHLTPGVFIGKGFEPGVTNILKTTQGSKIFLKEVND
  TLLVNELKSKESDIMTTNGVIHVVDKLLYPADTPVGNDQLLEILNKLIKYIQIKFVRGST
  FKEIPVTVYTTKIITKVVEPKIKVIEGSLQPIIKTEGPTLTKVKIEGEPEFRLIKEGETI
  TEVIHGEPIIKKYTKIIDGVPVEITEKETREERIITGPEIKYTRISTGGGETEETLKKLL
  QEEVTKVTKFIEGGDGHLFEDEEIKRLLQGDTPVRKLQANKKVQGSRRRLREGRSQ
• Function: Induces cell attachment and spreading and plays a role in cell adhesion. Enhances incorporation of BMP1 in the fibronectin matrix of connective tissues, and subsequent proteolytic activation of lysyl oxidase LOX.
• Tissue Specificity: Widely expressed with highest levels in aorta, stomach, lower gastrointestinal tract, placenta, uterus, thyroid tissue and breast. Expressed in the kidney . Expressed in the lung . Up-regulated in epithelial ovarian tumors. Not expressed in normal ovaries. Also highly expressed at the tumor periphery of lung carcinoma tissue but not within the tumor. Overexpressed in breast cancers.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Periostin (POSTN) decreases the response to substance of Cisplatin.	[24]
Methotrexate	DM2TEOL	Approved	Periostin (POSTN) decreases the response to substance of Methotrexate.	[24]
Fluorouracil	DMUM7HZ	Approved	Periostin (POSTN) decreases the response to substance of Fluorouracil.	[25]
Topotecan	DMP6G8T	Approved	Periostin (POSTN) decreases the response to substance of Topotecan.	[24]

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 Periostin (POSTN).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Periostin (POSTN).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Periostin (POSTN).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Periostin (POSTN).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Periostin (POSTN).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Periostin (POSTN).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Periostin (POSTN).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Periostin (POSTN).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Periostin (POSTN).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Periostin (POSTN).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Periostin (POSTN).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Periostin (POSTN).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Periostin (POSTN).	[12]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Periostin (POSTN).	[13]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Periostin (POSTN).	[14]
Rofecoxib	DM3P5DA	Approved	Rofecoxib affects the expression of Periostin (POSTN).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Periostin (POSTN).	[16]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Periostin (POSTN).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Periostin (POSTN).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Periostin (POSTN).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Periostin (POSTN).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Periostin (POSTN).	[22]
Erythropoietin	DM3R8YL	Investigative	Erythropoietin decreases the expression of Periostin (POSTN).	[23]

References

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• [3] 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.
• [4] Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes. Arch Toxicol. 2018 Jan;92(1):371-381.
• [5] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [6] 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.
• [7] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] 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.
• [10] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [13] Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch Toxicol. 2018 Apr;92(4):1507-1524.
• [14] Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009 Aug 21;138(4):645-659. doi: 10.1016/j.cell.2009.06.034. Epub 2009 Aug 13.
• [15] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis. Mol Cell Biochem. 2011 Nov;357(1-2):83-94. doi: 10.1007/s11010-011-0878-2. Epub 2011 May 19.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [20] 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.
• [21] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [22] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [23] Raloxifene and n-Acetylcysteine Ameliorate TGF-Signalling in Fibroblasts from Patients with Recessive Dominant Epidermolysis Bullosa. Cells. 2020 Sep 16;9(9):2108. doi: 10.3390/cells9092108.
• [24] Microarray-based detection and expression analysis of extracellular matrix proteins in drug?resistant ovarian cancer cell lines. Oncol Rep. 2014 Nov;32(5):1981-90. doi: 10.3892/or.2014.3468. Epub 2014 Sep 9.
• [25] Periostin induction in tumor cell line explants and inhibition of in vitro cell growth by anti-periostin antibodies. Carcinogenesis. 2005 May;26(5):908-15. doi: 10.1093/carcin/bgi034. Epub 2005 Feb 24.