Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8GZ0CA)

DOT Name	Secreted frizzled-related protein 2 (SFRP2)
Synonyms	FRP-2; sFRP-2; Secreted apoptosis-related protein 1; SARP-1
Gene Name	SFRP2
Related Disease	Liver cirrhosis ( ) Adenoma ( ) Advanced cancer ( ) Bone osteosarcoma ( ) Carcinoma ( ) Cervical cancer ( ) Cervical carcinoma ( ) Clear cell renal carcinoma ( ) Esophageal squamous cell carcinoma ( ) Gastric cancer ( ) Glioblastoma multiforme ( ) Hepatitis C virus infection ( ) Hepatocellular carcinoma ( ) Myocardial infarction ( ) Neoplasm ( ) Obesity ( ) Osteoarthritis ( ) Osteosarcoma ( ) Ovarian neoplasm ( ) Pancreatic tumour ( ) Papillary renal cell carcinoma ( ) Prostate cancer ( ) Prostate carcinoma ( ) Renal cell carcinoma ( ) Retinitis pigmentosa ( ) Rheumatoid arthritis ( ) Small lymphocytic lymphoma ( ) Squamous cell carcinoma ( ) Stomach cancer ( ) Ulcerative colitis ( ) Urinary bladder neoplasm ( ) Acute myelogenous leukaemia ( ) Adenocarcinoma ( ) Angiosarcoma ( ) Colorectal neoplasm ( ) Non-small-cell lung cancer ( ) Triple negative breast cancer ( ) Breast neoplasm ( ) Glioma ( ) Inflammatory bowel disease ( ) Melanoma ( ) Nasopharyngeal carcinoma ( ) Plasma cell myeloma ( )
UniProt ID	SFRP2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF01392 ; PF01759
Sequence	MLQGPGSLLLLFLASHCCLGSARGLFLFGQPDFSYKRSNCKPIPANLQLCHGIEYQNMRL PNLLGHETMKEVLEQAGAWIPLVMKQCHPDTKKFLCSLFAPVCLDDLDETIQPCHSLCVQ VKDRCAPVMSAFGFPWPDMLECDRFPQDNDLCIPLASSDHLLPATEEAPKVCEACKNKND DDNDIMETLCKNDFALKIKVKEITYINRDTKIILETKSKTIYKLNGVSERDLKKSVLWLK DSLQCTCEEMNDINAPYLVMGQKQGGELVITSVKRWQKGQREFKRISRSIRKLQC
Function	Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP2 may be important for eye retinal development and for myogenesis.
Tissue Specificity	Expressed in adipose tissue, heart, brain, skeletal muscle, pancreas, thymus, prostate, testis, ovary, small intestine and colon. Highest levels in adipose tissue, small intestine and colon.
KEGG Pathway	Wnt sig.ling pathway (hsa04310 )
Reactome Pathway	Negative regulation of TCF-dependent signaling by WNT ligand antagonists (R-HSA-3772470 ) TCF dependent signaling in response to WNT (R-HSA-201681 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Liver cirrhosis	DIS4G1GX	Definitive	Genetic Variation	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Posttranslational Modification	[10]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Myocardial infarction	DIS655KI	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Obesity	DIS47Y1K	Strong	Altered Expression	[13]
Osteoarthritis	DIS05URM	Strong	Biomarker	[14]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[4]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[6]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[15]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[16]
Prostate cancer	DISF190Y	Strong	Biomarker	[17]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[17]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[7]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[18]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[19]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Posttranslational Modification	[21]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[22]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[23]
Acute myelogenous leukaemia	DISCSPTN	moderate	Altered Expression	[24]
Adenocarcinoma	DIS3IHTY	moderate	Posttranslational Modification	[25]
Angiosarcoma	DISIYS9W	moderate	Biomarker	[26]
Colorectal neoplasm	DISR1UCN	moderate	Posttranslational Modification	[27]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[28]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[26]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[29]
Glioma	DIS5RPEH	Limited	Biomarker	[30]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[31]
Melanoma	DIS1RRCY	Limited	Biomarker	[32]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[33]
Plasma cell myeloma	DIS0DFZ0	Limited	Altered Expression	[34]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

14 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 Secreted frizzled-related protein 2 (SFRP2).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[37]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[39]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Secreted frizzled-related protein 2 (SFRP2).	[40]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Secreted frizzled-related protein 2 (SFRP2).	[41]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[42]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[43]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[44]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Secreted frizzled-related protein 2 (SFRP2).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[48]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[49]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Secreted frizzled-related protein 2 (SFRP2).	[50]
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⏷ Show the Full List of 14 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Secreted frizzled-related protein 2 (SFRP2).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Secreted frizzled-related protein 2 (SFRP2).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Secreted frizzled-related protein 2 (SFRP2).	[47]
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References

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2	DNA methylation changes and somatic mutations as tumorigenic events in Lynch syndrome-associated adenomas retaining mismatch repair protein expression.EBioMedicine. 2019 Jan;39:280-291. doi: 10.1016/j.ebiom.2018.12.018. Epub 2018 Dec 18.
3	Secreted Frizzled-Related Protein 2 Is Associated with Disease Progression and Poor Prognosis in Breast Cancer.Dis Markers. 2019 Mar 3;2019:6149381. doi: 10.1155/2019/6149381. eCollection 2019.
4	Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism.Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):E11128-E11137. doi: 10.1073/pnas.1814044115. Epub 2018 Nov 1.
5	Promoter hypermethylation of the SFRP2 gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer.Mol Cancer. 2008 Nov 6;7:83. doi: 10.1186/1476-4598-7-83.
6	SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway.Gynecol Oncol. 2009 Mar;112(3):646-53. doi: 10.1016/j.ygyno.2008.10.026. Epub 2008 Dec 18.
7	DNA methyltransferase inhibitor-mediated apoptosis in the Wnt/-catenin signal pathway in a renal cell carcinoma cell line.Exp Biol Med (Maywood). 2013 Sep;238(9):1009-16. doi: 10.1177/1535370213498984. Epub 2013 Aug 23.
8	The Silencing of SFRP2 Expression in ESCC Is Due to Methylation of the Gene Promoter.Technol Cancer Res Treat. 2019 Jan 1;18:1533033819877977. doi: 10.1177/1533033819877977.
9	Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer.Oncogene. 2007 Jul 12;26(32):4699-713. doi: 10.1038/sj.onc.1210259. Epub 2007 Feb 5.
10	Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behavior in a lineage-dependent manner.Genes Dev. 2013 Mar 15;27(6):654-69. doi: 10.1101/gad.212662.112.
11	miR-629-5p promotes growth and metastasis of hepatocellular carcinoma by activating -catenin.Exp Cell Res. 2019 Jul 15;380(2):124-130. doi: 10.1016/j.yexcr.2019.03.042. Epub 2019 Apr 4.
12	Insights from molecular signature of in vivo cardiac c-Kit(+) cells following cardiac injury and -catenin inhibition.J Mol Cell Cardiol. 2018 Oct;123:64-74. doi: 10.1016/j.yjmcc.2018.08.024. Epub 2018 Aug 29.
13	Tissue restricted expression of two human Frzbs in preadipocytes and pancreas.Biochem Biophys Res Commun. 1998 Jun 18;247(2):287-93. doi: 10.1006/bbrc.1998.8784.
14	Differential expression of WNTs and FRPs in the synovium of rheumatoid arthritis and osteoarthritis.Biochem Biophys Res Commun. 2006 Jul 14;345(4):1615-20. doi: 10.1016/j.bbrc.2006.05.075. Epub 2006 May 22.
15	TET1-mediated DNA hydroxymethylation activates inhibitors of the Wnt/-catenin signaling pathway to suppress EMT in pancreatic tumor cells.J Exp Clin Cancer Res. 2019 Aug 9;38(1):348. doi: 10.1186/s13046-019-1334-5.
16	DNA methylation and histone modifications cause silencing of Wnt antagonist gene in human renal cell carcinoma cell lines.Int J Cancer. 2008 Aug 1;123(3):535-42. doi: 10.1002/ijc.23514.
17	PHF21B overexpression promotes cancer stem cell-like traits in prostate cancer cells by activating the Wnt/-catenin signaling pathway.J Exp Clin Cancer Res. 2017 Jun 23;36(1):85. doi: 10.1186/s13046-017-0560-y.
18	Altered expression of secreted frizzled-related protein-2 in retinitis pigmentosa retinas.Invest Ophthalmol Vis Sci. 2000 May;41(6):1297-301.
19	Regulation of GRB2 and FLICE2 expression by TNF-alpha in rheumatoid synovium.Immunol Lett. 2003 Dec 15;90(2-3):93-6. doi: 10.1016/j.imlet.2003.07.002.
20	CpG island methylation patterns in chronic lymphocytic leukemia.Leuk Lymphoma. 2009 Mar;50(3):419-26. doi: 10.1080/10428190902756594.
21	Promoter methylation of SFRPs gene family in cervical cancer.Gynecol Oncol. 2009 Feb;112(2):301-6. doi: 10.1016/j.ygyno.2008.10.004. Epub 2008 Nov 26.
22	Hypermethylation of SFRP2 as a potential marker for stool-based detection of colorectal cancer and precancerous lesions.Dig Dis Sci. 2007 Sep;52(9):2287-91. doi: 10.1007/s10620-007-9755-y. Epub 2007 Apr 5.
23	Combination analysis of hypermethylated Wnt-antagonist family genes as a novel epigenetic biomarker panel for bladder cancer detection.Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2109-16. doi: 10.1158/1078-0432.CCR-05-2468.
24	Prognostic Significance of Secreted Frizzled-Related Protein 2 Expression in Cytogenetically Normal Primary Acute Myeloid Leukemia.Am J Med Sci. 2015 Nov;350(5):369-73. doi: 10.1097/MAJ.0000000000000567.
25	Synchronous alterations of Wnt and epidermal growth factor receptor signaling pathways through aberrant methylation and mutation in non small cell lung cancer.Clin Cancer Res. 2007 Oct 15;13(20):6087-92. doi: 10.1158/1078-0432.CCR-07-0591.
26	Development of a Novel Humanized Monoclonal Antibody to Secreted Frizzled-Related Protein-2 That Inhibits Triple-Negative Breast Cancer and Angiosarcoma Growth In Vivo.Ann Surg Oncol. 2019 Dec;26(13):4782-4790. doi: 10.1245/s10434-019-07800-2. Epub 2019 Sep 12.
27	Silencing of secreted frizzled-related protein genes in MSI colorectal carcinogenesis.Hepatogastroenterology. 2008 Jul-Aug;55(85):1265-8.
28	SFRP2 modulates nonsmall cell lung cancer A549cell apoptosis and metastasis by regulating mitochondrial fission via Wnt pathways.Mol Med Rep. 2019 Aug;20(2):1925-1932. doi: 10.3892/mmr.2019.10393. Epub 2019 Jun 18.
29	Secreted frizzle-related protein 2 stimulates angiogenesis via a calcineurin/NFAT signaling pathway.Cancer Res. 2009 Jun 1;69(11):4621-8. doi: 10.1158/0008-5472.CAN-08-3402. Epub 2009 May 19.
30	Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells.Oncogene. 2000 Aug 31;19(37):4210-20. doi: 10.1038/sj.onc.1203783.
31	MGMT-B gene promoter hypermethylation in patients with inflammatory bowel disease - a novel finding.Asian Pac J Cancer Prev. 2015;16(5):1945-52. doi: 10.7314/apjcp.2015.16.5.1945.
32	sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance.Nature. 2016 Apr 14;532(7598):250-4. doi: 10.1038/nature17392. Epub 2016 Apr 4.
33	TET1 exerts its anti-tumor functions via demethylating DACT2 and SFRP2 to antagonize Wnt/-catenin signaling pathway in nasopharyngeal carcinoma cells.Clin Epigenetics. 2018 Aug 3;10(1):103. doi: 10.1186/s13148-018-0535-7.
34	Sclerostin is overexpressed by plasma cells from multiple myeloma patients.Ann N Y Acad Sci. 2011 Nov;1237:19-23. doi: 10.1111/j.1749-6632.2011.06196.x.
35	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
36	Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
37	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.
38	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
39	Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
40	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
41	Wnt signaling pathway is epigenetically regulated by methylation of Wnt antagonists in acute myeloid leukemia. Leukemia. 2009 Sep;23(9):1658-66. doi: 10.1038/leu.2009.86. Epub 2009 Apr 23.
42	Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
43	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.
44	Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
45	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.
46	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.
47	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
48	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.
49	Deguelin inhibits growth of breast cancer cells by modulating the expression of key members of the Wnt signaling pathway. Cancer Prev Res (Phila). 2009 Nov;2(11):942-50. doi: 10.1158/1940-6207.CAPR-08-0232. Epub 2009 Oct 27.
50	Lithium chloride regulates the proliferation of stem-like cells in retinoblastoma cell lines: a potential role for the canonical Wnt signaling pathway. Mol Vis. 2010 Jan 13;16:36-45.