Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXFFY56)

• DOT Name: Frizzled-5 (FZD5)
• Synonyms: Fz-5; hFz5; FzE5
• Gene Name: FZD5
• Related Disease:
  Acute myelogenous leukaemia
  Gastric neoplasm
  Adenoma
  Advanced cancer
  Alzheimer disease
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Clear cell renal carcinoma
  Coloboma of optic nerve
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Depression
  Familial adenomatous polyposis
  Hypertrophic cardiomyopathy
  Kidney neoplasm
  Myopia
  Myotonic dystrophy type 1
  Osteosarcoma
  Psoriasis
  Renal cell carcinoma
  Schizophrenia
  Synovitis
  Type-1/2 diabetes
  Ulcerative colitis
  Arteriosclerosis
  Atherosclerosis
  Exudative vitreoretinopathy
  Metastatic malignant neoplasm
  Neoplasm
  Neuroblastoma
  Obesity
  Prostate cancer
  Prostate carcinoma
  Hepatocellular carcinoma
  Non-small-cell lung cancer
  Childhood kidney Wilms tumor
  Colorectal carcinoma
  Matthew-Wood syndrome
  Microphthalmia
  Triple negative breast cancer
  Wilms tumor
• UniProt ID: FZD5_HUMAN
• PDB ID: 5URY; 5URZ; 6O39; 6WW2
• Pfam ID: PF01534 ; PF01392
• Sequence:
  MARPDPSAPPSLLLLLLAQLVGRAAAASKAPVCQEITVPMCRGIGYNLTHMPNQFNHDTQ
  DEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLPDYHKPLPPCRSVCERAKAGCSPLM
  RQYGFAWPERMSCDRLPVLGRDAEVLCMDYNRSEATTAPPRPFPAKPTLPGPPGAPASGG
  ECPAGGPFVCKCREPFVPILKESHPLYNKVRTGQVPNCAVPCYQPSFSADERTFATFWIG
  LWSVLCFISTSTTVATFLIDMERFRYPERPIIFLSACYLCVSLGFLVRLVVGHASVACSR
  EHNHIHYETTGPALCTIVFLLVYFFGMASSIWWVILSLTWFLAAGMKWGNEAIAGYAQYF
  HLAAWLIPSVKSITALALSSVDGDPVAGICYVGNQNLNSLRGFVLGPLVLYLLVGTLFLL
  AGFVSLFRIRSVIKQGGTKTDKLEKLMIRIGIFTLLYTVPASIVVACYLYEQHYRESWEA
  ALTCACPGHDTGQPRAKPEYWVLMLKYFMCLVVGITSGVWIWSGKTVESWRRFTSRCCCR
  PRRGHKSGGAMAAGDYPEASAALTGRTGPPGPAATYHKQVSLSHV
• Function: Receptor for Wnt proteins. Can activate WNT2, WNT10B, WNT5A, but not WNT2B or WNT4 (in vitro); the in vivo situation may be different since not all of these are known to be coexpressed. In neurons, activation of WNT7A promotes formation of synapses. Functions in the canonical Wnt/beta-catenin signaling pathway. The canonical Wnt/beta-catenin signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues (Probable). Plays a role in yolk sac angiogenesis and in placental vascularization.
• KEGG Pathway:
  mTOR sig.ling pathway (hsa04150)
  Wnt sig.ling pathway (hsa04310)
  Hippo sig.ling pathway (hsa04390)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Melanogenesis (hsa04916)
  Cushing syndrome (hsa04934)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Basal cell carcinoma (hsa05217)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  Ca2+ pathway (R-HSA-4086398)
  Asymmetric localization of PCP proteins (R-HSA-4608870)
  Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262)
  Regulation of FZD by ubiquitination (R-HSA-4641263)
  WNT5A-dependent internalization of FZD2, FZD5 and ROR2 (R-HSA-5140745)
  Signaling by RNF43 mutants (R-HSA-5340588)
  Class B/2 (Secretin family receptors) (R-HSA-373080)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Gastric neoplasm	DISOKN4Y	Definitive	Altered Expression	[2]
Adenoma	DIS78ZEV	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[5]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Coloboma of optic nerve	DISR9DCH	Strong	GermlineCausalMutation	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[12]
Depression	DIS3XJ69	Strong	Biomarker	[13]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[14]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Altered Expression	[15]
Kidney neoplasm	DISBNZTN	Strong	Altered Expression	[8]
Myopia	DISK5S60	Strong	Altered Expression	[16]
Myotonic dystrophy type 1	DISJC0OX	Strong	Biomarker	[17]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[6]
Psoriasis	DIS59VMN	Strong	Biomarker	[18]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[9]
Schizophrenia	DISSRV2N	Strong	Biomarker	[19]
Synovitis	DISW2GPY	Strong	Biomarker	[20]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[17]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[21]
Arteriosclerosis	DISK5QGC	moderate	Altered Expression	[22]
Atherosclerosis	DISMN9J3	moderate	Altered Expression	[22]
Exudative vitreoretinopathy	DISWN0TG	moderate	Genetic Variation	[23]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[24]
Neoplasm	DISZKGEW	moderate	Biomarker	[24]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[25]
Obesity	DIS47Y1K	moderate	Altered Expression	[22]
Prostate cancer	DISF190Y	moderate	Biomarker	[26]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[26]
Hepatocellular carcinoma	DIS0J828	Disputed	Biomarker	[27]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Altered Expression	[28]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[29]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[30]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[31]
Microphthalmia	DISGEBES	Limited	Biomarker	[32]
Triple negative breast cancer	DISAMG6N	Limited	Genetic Variation	[33]
Wilms tumor	DISB6T16	Limited	Biomarker	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Frizzled-5 (FZD5).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Frizzled-5 (FZD5).	[55]

29 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 Frizzled-5 (FZD5).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Frizzled-5 (FZD5).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Frizzled-5 (FZD5).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Frizzled-5 (FZD5).	[38]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Frizzled-5 (FZD5).	[39]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Frizzled-5 (FZD5).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Frizzled-5 (FZD5).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Frizzled-5 (FZD5).	[42]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Frizzled-5 (FZD5).	[43]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Frizzled-5 (FZD5).	[42]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Frizzled-5 (FZD5).	[44]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Frizzled-5 (FZD5).	[45]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Frizzled-5 (FZD5).	[43]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Frizzled-5 (FZD5).	[46]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Frizzled-5 (FZD5).	[47]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Frizzled-5 (FZD5).	[48]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Frizzled-5 (FZD5).	[44]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of Frizzled-5 (FZD5).	[49]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid increases the expression of Frizzled-5 (FZD5).	[50]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Frizzled-5 (FZD5).	[51]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Frizzled-5 (FZD5).	[52]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Frizzled-5 (FZD5).	[43]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Frizzled-5 (FZD5).	[39]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Frizzled-5 (FZD5).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Frizzled-5 (FZD5).	[53]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Frizzled-5 (FZD5).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Frizzled-5 (FZD5).	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Frizzled-5 (FZD5).	[57]
Cordycepin	DM72Y01	Investigative	Cordycepin increases the expression of Frizzled-5 (FZD5).	[49]

References

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