Details of Drug Off-Target (DOT)

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

• DOT Name: DNA excision repair protein ERCC-1 (ERCC1)
• Gene Name: ERCC1
• Related Disease:
  Bladder cancer
  Cerebrooculofacioskeletal syndrome 4
  Embryonal neoplasm
  Germ cell tumor
  Head and neck carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Alcohol use disorder
  Benign neoplasm
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Cervical carcinoma
  Colon cancer
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Fanconi's anemia
  Gastric neoplasm
  Hepatocellular carcinoma
  Hereditary diffuse gastric adenocarcinoma
  Leukopenia
  Lung adenocarcinoma
  Lung neoplasm
  Metastatic malignant neoplasm
  Myotonic dystrophy
  Nasopharyngeal carcinoma
  Neoplasm of esophagus
  Neoplasm of testis
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Small-cell lung cancer
  Testicular cancer
  Xeroderma pigmentosum group F
  XFE progeroid syndrome
  Adult glioblastoma
  Cervical cancer
  Triple negative breast cancer
  Xeroderma pigmentosum group A
  Cockayne syndrome type 2
  COFS syndrome
  B-cell neoplasm
  Chromosomal disorder
  Colon carcinoma
  Glioblastoma multiforme
  Head and neck cancer
  Uterine cervix neoplasm
• UniProt ID: ERCC1_HUMAN
• PDB ID: 1Z00; 2A1I; 2A1J; 2JNW; 2JPD; 2MUT; 6SXA; 6SXB
• Pfam ID: PF14520 ; PF03834
• Sequence:
  MDPGKDKEGVPQPSGPPARKKFVIPLDEDEVPPGVAKPLFRSTQSLPTVDTSAQAAPQTY
  AEYAISQPLEGAGATCPTGSEPLAGETPNQALKPGAKSNSIIVSPRQRGNPVLKFVRNVP
  WEFGDVIPDYVLGQSTCALFLSLRYHNLHPDYIHGRLQSLGKNFALRVLLVQVDVKDPQQ
  ALKELAKMCILADCTLILAWSPEEAGRYLETYKAYEQKPADLLMEKLEQDFVSRVTECLT
  TVKSVNKTDSQTLLTTFGSLEQLIAASREDLALCPGLGPQKARRLFDVLHEPFLKVP
• Function: [Isoform 1]: Non-catalytic component of a structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair. Responsible, in conjunction with SLX4, for the first step in the repair of interstrand cross-links (ICL). Participates in the processing of anaphase bridge-generating DNA structures, which consist in incompletely processed DNA lesions arising during S or G2 phase, and can result in cytokinesis failure. Also required for homology-directed repair (HDR) of DNA double-strand breaks, in conjunction with SLX4; [Isoform 2]: Not functional in the nucleotide excision repair pathway; [Isoform 3]: Not functional in the nucleotide excision repair pathway; [Isoform 4]: Not functional in the nucleotide excision repair pathway.
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  Nucleotide excision repair (hsa03420)
  Fanconi anemia pathway (hsa03460)
• Reactome Pathway:
  Formation of Incision Complex in GG-NER (R-HSA-5696395)
  Dual Incision in GG-NER (R-HSA-5696400)
  Dual incision in TC-NER (R-HSA-6782135)
  Fanconi Anemia Pathway (R-HSA-6783310)
  HDR through Single Strand Annealing (SSA) (R-HSA-5685938)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Definitive	Biomarker	[1]
Cerebrooculofacioskeletal syndrome 4	DIS80U6W	Definitive	Autosomal recessive	[2]
Embryonal neoplasm	DIS5MQSB	Definitive	Biomarker	[3]
Germ cell tumor	DIS62070	Definitive	Biomarker	[3]
Head and neck carcinoma	DISOU1DS	Definitive	Altered Expression	[4]
Urinary bladder cancer	DISDV4T7	Definitive	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Definitive	Biomarker	[1]
Alcohol use disorder	DISMB65Y	Strong	Biomarker	[5]
Benign neoplasm	DISDUXAD	Strong	Posttranslational Modification	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[9]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[9]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[12]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[13]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[15]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[14]
Leukopenia	DISJMBMM	Strong	Genetic Variation	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Lung neoplasm	DISVARNB	Strong	Biomarker	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[19]
Myotonic dystrophy	DISNBEMX	Strong	Biomarker	[20]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[21]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[9]
Neoplasm of testis	DISK4XHT	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[22]
Prostate cancer	DISF190Y	Strong	Altered Expression	[23]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[23]
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[24]
Testicular cancer	DIS6HNYO	Strong	Biomarker	[3]
Xeroderma pigmentosum group F	DISRKRYY	Strong	Biomarker	[25]
XFE progeroid syndrome	DISVZ5JW	Strong	Biomarker	[26]
Adult glioblastoma	DISVP4LU	moderate	Genetic Variation	[27]
Cervical cancer	DISFSHPF	moderate	Altered Expression	[10]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[28]
Xeroderma pigmentosum group A	DIS38HWC	moderate	Biomarker	[29]
Cockayne syndrome type 2	DIS3X0GQ	Supportive	Autosomal recessive	[30]
COFS syndrome	DISTEABI	Supportive	Autosomal recessive	[2]
B-cell neoplasm	DISVY326	Limited	Altered Expression	[31]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[32]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[33]
Head and neck cancer	DISBPSQZ	Limited	Altered Expression	[4]
Uterine cervix neoplasm	DIS0BYVV	Limited	Biomarker	[34]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Gefitinib	DM15F0X	Approved	DNA excision repair protein ERCC-1 (ERCC1) affects the response to substance of Gefitinib.	[65]
Resveratrol	DM3RWXL	Phase 3	DNA excision repair protein ERCC-1 (ERCC1) affects the response to substance of Resveratrol.	[52]

35 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 DNA excision repair protein ERCC-1 (ERCC1).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[40]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[41]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[42]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[43]
Triclosan	DMZUR4N	Approved	Triclosan affects the expression of DNA excision repair protein ERCC-1 (ERCC1).	[44]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[41]
Selenium	DM25CGV	Approved	Selenium increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[45]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[46]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[47]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[48]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[49]
Melatonin	DMKWFBT	Approved	Melatonin increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[50]
Ximelegatran	DMU8ANS	Approved	Ximelegatran increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[51]
Pemetrexed	DMMX2E6	Approved	Pemetrexed decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[52]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[53]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[54]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[55]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[45]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[56]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[43]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[58]
SB 203580	DMAET6F	Terminated	SB 203580 increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[59]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[60]
Paraquat	DMR8O3X	Investigative	Paraquat affects the splicing of DNA excision repair protein ERCC-1 (ERCC1).	[61]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[59]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[62]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[63]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[64]
3-aminobenzamide	DM7P3IZ	Investigative	3-aminobenzamide decreases the expression of DNA excision repair protein ERCC-1 (ERCC1).	[59]

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 DNA excision repair protein ERCC-1 (ERCC1).	[57]

References

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