Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6QGG7O)

• DOT Name: Flap endonuclease 1 (FEN1)
• Synonyms: FEN-1; EC 3.1.-.-; DNase IV; Flap structure-specific endonuclease 1; Maturation factor 1; MF1; hFEN-1
• Gene Name: FEN1
• Related Disease:
  Bone osteosarcoma
  Epithelial ovarian cancer
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Adult glioblastoma
  Advanced cancer
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal neoplasm
  Endometrial carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Huntington disease
  leukaemia
  Matthew-Wood syndrome
  Neoplasm
  Stomach cancer
  Systemic lupus erythematosus
  Werner syndrome
  Breast neoplasm
  Lung adenocarcinoma
  Lung neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Xeroderma pigmentosum group G
  Colorectal carcinoma
  Coronary atherosclerosis
  Coronary heart disease
  Crohn disease
  Familial adenomatous polyposis
  Inflammatory bowel disease
• UniProt ID: FEN1_HUMAN
• PDB ID: 1U7B; 1UL1; 3Q8K; 3Q8L; 3Q8M; 3UVU; 5E0V; 5FV7; 5K97; 5KSE; 5UM9; 5ZOD; 5ZOE; 5ZOF; 5ZOG; 6TNZ; 7QO1
• EC Number: 3.1.-.-
• Pfam ID: PF00867 ; PF00752
• Sequence:
  MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGGDVLQNEEGET
  TSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKRSERRAEAEKQLQQAQAAGAE
  QEVEKFTKRLVKVTKQHNDECKHLLSLMGIPYLDAPSEAEASCAALVKAGKVYAAATEDM
  DCLTFGSPVLMRHLTASEAKKLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRG
  IGPKRAVDLIQKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSE
  PNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTQGRLDDFFKVTGSLSSAKRKEPEP
  KGSTKKKAKTGAAGKFKRGK
• Function: Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.
• KEGG Pathway:
  D. replication (hsa03030)
  Base excision repair (hsa03410)
  Non-homologous end-joining (hsa03450)
• Reactome Pathway:
  Early Phase of HIV Life Cycle (R-HSA-162594)
  Removal of the Flap Intermediate from the C-strand (R-HSA-174437)
  PCNA-Dependent Long Patch Base Excision Repair (R-HSA-5651801)
  HDR through MMEJ (alt-NHEJ) (R-HSA-5685939)
  Removal of the Flap Intermediate (R-HSA-69166)
  POLB-Dependent Long Patch Base Excision Repair (R-HSA-110362)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Altered Expression	[1]
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[2]
Osteosarcoma	DISLQ7E2	Definitive	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Genetic Variation	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[8]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[7]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[7]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[7]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[9]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[10]
Gastric cancer	DISXGOUK	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Genetic Variation	[12]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Huntington disease	DISQPLA4	Strong	Biomarker	[15]
leukaemia	DISS7D1V	Strong	Genetic Variation	[12]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Altered Expression	[14]
Stomach cancer	DISKIJSX	Strong	Biomarker	[11]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[17]
Werner syndrome	DISZY45W	Strong	Biomarker	[18]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[19]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[20]
Lung neoplasm	DISVARNB	moderate	Biomarker	[21]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[22]
Prostate cancer	DISF190Y	moderate	Altered Expression	[23]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[23]
Xeroderma pigmentosum group G	DIS4PV33	Disputed	Biomarker	[24]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[7]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[25]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[25]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[26]
Familial adenomatous polyposis	DISW53RE	Limited	Biomarker	[27]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Flap endonuclease 1 (FEN1) affects the response to substance of Vinblastine.	[63]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Flap endonuclease 1 (FEN1).	[29]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Flap endonuclease 1 (FEN1).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Flap endonuclease 1 (FEN1).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Flap endonuclease 1 (FEN1).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Flap endonuclease 1 (FEN1).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Flap endonuclease 1 (FEN1).	[34]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Flap endonuclease 1 (FEN1).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Flap endonuclease 1 (FEN1).	[36]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Flap endonuclease 1 (FEN1).	[37]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Flap endonuclease 1 (FEN1).	[38]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Flap endonuclease 1 (FEN1).	[38]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Flap endonuclease 1 (FEN1).	[39]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Flap endonuclease 1 (FEN1).	[37]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Flap endonuclease 1 (FEN1).	[40]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Flap endonuclease 1 (FEN1).	[41]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Flap endonuclease 1 (FEN1).	[42]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Flap endonuclease 1 (FEN1).	[43]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Flap endonuclease 1 (FEN1).	[44]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Flap endonuclease 1 (FEN1).	[45]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Flap endonuclease 1 (FEN1).	[46]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Flap endonuclease 1 (FEN1).	[47]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Flap endonuclease 1 (FEN1).	[48]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Flap endonuclease 1 (FEN1).	[35]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Flap endonuclease 1 (FEN1).	[49]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Flap endonuclease 1 (FEN1).	[50]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Flap endonuclease 1 (FEN1).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Flap endonuclease 1 (FEN1).	[52]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Flap endonuclease 1 (FEN1).	[53]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Flap endonuclease 1 (FEN1).	[54]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Flap endonuclease 1 (FEN1).	[56]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Flap endonuclease 1 (FEN1).	[57]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Flap endonuclease 1 (FEN1).	[58]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Flap endonuclease 1 (FEN1).	[59]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Flap endonuclease 1 (FEN1).	[60]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 decreases the expression of Flap endonuclease 1 (FEN1).	[61]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Flap endonuclease 1 (FEN1).	[62]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Flap endonuclease 1 (FEN1).	[55]

References

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