Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTO3DPY)

• DOT Name: Secreted frizzled-related protein 3 (FRZB)
• Synonyms: sFRP-3; Frezzled; Fritz; Frizzled-related protein 1; FrzB-1
• Gene Name: FRZB
• Related Disease:
  Adult glioblastoma
  Advanced cancer
  Gastric neoplasm
  Glioblastoma multiforme
  Arthritis
  Autosomal recessive limb-girdle muscular dystrophy type 2A
  Barrett esophagus
  Bone osteosarcoma
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Clear cell renal carcinoma
  Colorectal neoplasm
  Congestive heart failure
  Dilated cardiomyopathy 1A
  Esophageal adenocarcinoma
  Hepatocellular carcinoma
  Kidney cancer
  Medulloblastoma
  Melanoma
  Myelodysplastic syndrome
  Non-small-cell lung cancer
  Osteoporosis
  Osteosarcoma
  Pancreatic cancer
  Plasma cell myeloma
  Renal carcinoma
  Renal cell carcinoma
  Retinitis pigmentosa
  Sarcoma
  Small lymphocytic lymphoma
  Squamous cell carcinoma
  Acute myelogenous leukaemia
  Adenocarcinoma
  Bone disease
  Cervical cancer
  Cervical carcinoma
  Colorectal adenoma
  Gastric cancer
  Leukemia
  Lung adenocarcinoma
  Mesothelioma
  Stomach cancer
• UniProt ID: SFRP3_HUMAN
• Pfam ID: PF01392 ; PF01759
• Sequence:
  MVCGSPGGMLLLRAGLLALAALCLLRVPGARAAACEPVRIPLCKSLPWNMTKMPNHLHHS
  TQANAILAIEQFEGLLGTHCSPDLLFFLCAMYAPICTIDFQHEPIKPCKSVCERARQGCE
  PILIKYRHSWPENLACEELPVYDRGVCISPEAIVTADGADFPMDSSNGNCRGASSERCKC
  KPIRATQKTYFRNNYNYVIRAKVKEIKTKCHDVTAVVEVKEILKSSLVNIPRDTVNLYTS
  SGCLCPPLNVNEEYIIMGYEDEERSRLLLVEGSIAEKWKDRLGKKVKRWDMKLRHLGLSK
  SDSSNSDSTQSQKSGRNSNPRQARN
• 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. SFRP3/FRZB appears to be involved in limb skeletogenesis. Antagonist of Wnt8 signaling. Regulates chondrocyte maturation and long bone development.
• Tissue Specificity: Expressed primarily in the cartilaginous cores of the long bone during embryonic and fetal development and in the appendicular skeleton (6-13 weeks). At 13 weeks of gestation, transcripts were present in early chondroblasts of the tarsal bones of the foot, the carpal bones of the hands and the epiphysis of long bones. Highly expressed in placenta and heart, followed by brain, skeletal muscle, kidney and pancreas. Weakly expressed in lung and liver.
• KEGG Pathway: Wnt sig.ling pathway (hsa04310)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[2]
Gastric neoplasm	DISOKN4Y	Definitive	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Arthritis	DIST1YEL	Strong	Genetic Variation	[4]
Autosomal recessive limb-girdle muscular dystrophy type 2A	DISIHX4S	Strong	Altered Expression	[5]
Barrett esophagus	DIS416Y7	Strong	Posttranslational Modification	[6]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[7]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[8]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[9]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[9]
Cardiac failure	DISDC067	Strong	Altered Expression	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[12]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[10]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[13]
Esophageal adenocarcinoma	DISODWFP	Strong	Posttranslational Modification	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[14]
Kidney cancer	DISBIPKM	Strong	Biomarker	[11]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[15]
Melanoma	DIS1RRCY	Strong	Posttranslational Modification	[14]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[14]
Osteoporosis	DISF2JE0	Strong	Genetic Variation	[17]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[7]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[18]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[19]
Renal carcinoma	DISER9XT	Strong	Biomarker	[11]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[11]
Retinitis pigmentosa	DISCGPY8	Strong	Altered Expression	[20]
Sarcoma	DISZDG3U	Strong	Biomarker	[21]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[14]
Acute myelogenous leukaemia	DISCSPTN	Limited	Posttranslational Modification	[23]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[14]
Bone disease	DISE1F82	Limited	Altered Expression	[19]
Cervical cancer	DISFSHPF	Limited	Altered Expression	[24]
Cervical carcinoma	DIST4S00	Limited	Altered Expression	[24]
Colorectal adenoma	DISTSVHM	Limited	Genetic Variation	[25]
Gastric cancer	DISXGOUK	Limited	Biomarker	[26]
Leukemia	DISNAKFL	Limited	Posttranslational Modification	[23]
Lung adenocarcinoma	DISD51WR	Limited	Biomarker	[14]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[27]
Stomach cancer	DISKIJSX	Limited	Biomarker	[26]

24 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 3 (FRZB).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[29]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[30]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Secreted frizzled-related protein 3 (FRZB).	[31]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Secreted frizzled-related protein 3 (FRZB).	[32]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Secreted frizzled-related protein 3 (FRZB).	[33]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[34]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Secreted frizzled-related protein 3 (FRZB).	[35]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[34]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Secreted frizzled-related protein 3 (FRZB).	[36]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[37]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Secreted frizzled-related protein 3 (FRZB).	[38]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[39]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Secreted frizzled-related protein 3 (FRZB).	[40]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Secreted frizzled-related protein 3 (FRZB).	[41]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Secreted frizzled-related protein 3 (FRZB).	[42]
Rofecoxib	DM3P5DA	Approved	Rofecoxib affects the expression of Secreted frizzled-related protein 3 (FRZB).	[42]
Benzylpenicillin	DMS9503	Phase 3	Benzylpenicillin decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[43]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[41]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[46]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Secreted frizzled-related protein 3 (FRZB).	[47]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Secreted frizzled-related protein 3 (FRZB).	[48]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Secreted frizzled-related protein 3 (FRZB).	[49]

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 Secreted frizzled-related protein 3 (FRZB).	[44]

References

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