Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0U9G41)

• DOT Name: Secreted frizzled-related protein 1 (SFRP1)
• Synonyms: FRP-1; sFRP-1; Secreted apoptosis-related protein 2; SARP-2
• Gene Name: SFRP1
• Related Disease:
  Adenoma
  Glioma
  Pancreatic tumour
  Precancerous condition
  Urinary bladder neoplasm
  Advanced cancer
  Bipolar disorder
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac disease
  Cholangiocarcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Depression
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Leiomyoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Meningioma
  Metastatic malignant neoplasm
  Narcolepsy
  Non-small-cell lung cancer
  Obesity
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Small lymphocytic lymphoma
  Squamous cell carcinoma
  Stomach cancer
  Urinary bladder cancer
  Uterine fibroids
  Acute myelogenous leukaemia
  Carcinoma
  Gastric cancer
  Medulloblastoma
  Colon cancer
  Adenocarcinoma
  Clear cell renal carcinoma
  Familial adenomatous polyposis
  Neuroblastoma
  Pancreatic cancer
  Renal cell carcinoma
• UniProt ID: SFRP1_HUMAN
• Pfam ID: PF01392 ; PF01759
• Sequence:
  MGIGRSEGGRRGAALGVLLALGAALLAVGSASEYDYVSFQSDIGPYQSGRFYTKPPQCVD
  IPADLRLCHNVGYKKMVLPNLLEHETMAEVKQQASSWVPLLNKNCHAGTQVFLCSLFAPV
  CLDRPIYPCRWLCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGDVCIAMTPPNATEASKP
  QGTTVCPPCDNELKSEAIIEHLCASEFALRMKIKEVKKENGDKKIVPKKKKPLKLGPIKK
  KDLKKLVLYLKNGADCPCHQLDNLSHHFLIMGRKVKSQYLLTAIHKWDKKNKEFKNFMKK
  MKNHECPTFQSVFK
• 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. SFRP1 decreases intracellular beta-catenin levels. Has antiproliferative effects on vascular cells, in vitro and in vivo, and can induce, in vivo, an angiogenic response. In vascular cell cycle, delays the G1 phase and entry into the S phase. In kidney development, inhibits tubule formation and bud growth in metanephroi. Inhibits WNT1/WNT4-mediated TCF-dependent transcription.
• Tissue Specificity: Widely expressed. Absent from lung, liver and peripheral blood leukocytes. Highest levels in heart and fetal kidney. Also expressed in testis, ovary, fetal brain and lung, leiomyomal cells, myometrial cells and vascular smooth muscle cells. Expressed in foreskin fibroblasts and in keratinocytes.
• 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

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Definitive	Biomarker	[1]
Glioma	DIS5RPEH	Definitive	Altered Expression	[2]
Pancreatic tumour	DIS3U0LK	Definitive	Posttranslational Modification	[3]
Precancerous condition	DISV06FL	Definitive	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Definitive	Altered Expression	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[7]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[8]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[9]
Cardiac disease	DISVO1I5	Strong	Biomarker	[6]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[11]
Colorectal neoplasm	DISR1UCN	Strong	Posttranslational Modification	[12]
Depression	DIS3XJ69	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[15]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Altered Expression	[18]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[18]
Meningioma	DISPT4TG	Strong	Altered Expression	[19]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[20]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[22]
Obesity	DIS47Y1K	Strong	Altered Expression	[23]
Osteoarthritis	DIS05URM	Strong	Biomarker	[24]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[13]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[13]
Prostate cancer	DISF190Y	Strong	Biomarker	[25]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[25]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[26]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[27]
Stomach cancer	DISKIJSX	Strong	Biomarker	[28]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[5]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[16]
Acute myelogenous leukaemia	DISCSPTN	moderate	Altered Expression	[29]
Carcinoma	DISH9F1N	moderate	Biomarker	[30]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[31]
Medulloblastoma	DISZD2ZL	moderate	Biomarker	[32]
Colon cancer	DISVC52G	Disputed	Posttranslational Modification	[33]
Adenocarcinoma	DIS3IHTY	Limited	Posttranslational Modification	[34]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[35]
Familial adenomatous polyposis	DISW53RE	Limited	Genetic Variation	[36]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[37]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[38]
Renal cell carcinoma	DISQZ2X8	Limited	Posttranslational Modification	[39]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Secreted frizzled-related protein 1 (SFRP1) affects the response to substance of Topotecan.	[66]

5 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 frizzled-related protein 1 (SFRP1).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the methylation of Secreted frizzled-related protein 1 (SFRP1).	[46]
Folic acid	DMEMBJC	Approved	Folic acid increases the methylation of Secreted frizzled-related protein 1 (SFRP1).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Secreted frizzled-related protein 1 (SFRP1).	[58]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Secreted frizzled-related protein 1 (SFRP1).	[60]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[43]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[44]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Secreted frizzled-related protein 1 (SFRP1).	[45]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[47]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Secreted frizzled-related protein 1 (SFRP1).	[48]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Secreted frizzled-related protein 1 (SFRP1).	[49]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[47]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Secreted frizzled-related protein 1 (SFRP1).	[50]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[52]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Secreted frizzled-related protein 1 (SFRP1).	[53]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Secreted frizzled-related protein 1 (SFRP1).	[54]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Secreted frizzled-related protein 1 (SFRP1).	[55]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Secreted frizzled-related protein 1 (SFRP1).	[56]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[57]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[59]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[61]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Secreted frizzled-related protein 1 (SFRP1).	[62]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Secreted frizzled-related protein 1 (SFRP1).	[63]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Secreted frizzled-related protein 1 (SFRP1).	[64]
Choline	DM5D9YK	Investigative	Choline affects the expression of Secreted frizzled-related protein 1 (SFRP1).	[65]

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