Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAHLB62)

• DOT Name: DNA replication licensing factor MCM5 (MCM5)
• Synonyms: EC 3.6.4.12; CDC46 homolog; P1-CDC46
• Gene Name: MCM5
• Related Disease:
  Bladder cancer
  Bladder transitional cell carcinoma
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Dyspepsia
  Esophageal cancer
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adenocarcinoma
  Advanced cancer
  Alcohol use disorder
  Cervical cancer
  Cervical carcinoma
  Cervical Intraepithelial neoplasia
  Colonic neoplasm
  Dysplasia of cervix
  Familial multiple trichoepithelioma
  Gastric adenocarcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Meier-Gorlin syndrome
  Prostate cancer
  Prostate carcinoma
  Skin disease
  Thyroid gland papillary carcinoma
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Clear cell renal carcinoma
  Meningioma
  Mungan syndrome
  Renal cell carcinoma
  Desmoid tumour
  Hepatocellular carcinoma
  Meier-Gorlin syndrome 8
• UniProt ID: MCM5_HUMAN
• PDB ID: 6XTX; 6XTY; 7PFO; 7PLO; 7W1Y; 7W68; 8B9D
• EC Number: 3.6.4.12
• Pfam ID: PF00493 ; PF17855 ; PF14551 ; PF17207
• Sequence:
  MSGFDDPGIFYSDSFGGDAQADEGQARKSQLQRRFKEFLRQYRVGTDRTGFTFKYRDELK
  RHYNLGEYWIEVEMEDLASFDEDLADYLYKQPAEHLQLLEEAAKEVADEVTRPRPSGEEV
  LQDIQVMLKSDASPSSIRSLKSDMMSHLVKIPGIIIAASAVRAKATRISIQCRSCRNTLT
  NIAMRPGLEGYALPRKCNTDQAGRPKCPLDPYFIMPDKCKCVDFQTLKLQELPDAVPHGE
  MPRHMQLYCDRYLCDKVVPGNRVTIMGIYSIKKFGLTTSRGRDRVGVGIRSSYIRVLGIQ
  VDTDGSGRSFAGAVSPQEEEEFRRLAALPNVYEVISKSIAPSIFGGTDMKKAIACLLFGG
  SRKRLPDGLTRRGDINLLMLGDPGTAKSQLLKFVEKCSPIGVYTSGKGSSAAGLTASVMR
  DPSSRNFIMEGGAMVLADGGVVCIDEFDKMREDDRVAIHEAMEQQTISIAKAGITTTLNS
  RCSVLAAANSVFGRWDETKGEDNIDFMPTILSRFDMIFIVKDEHNEERDVMLAKHVITLH
  VSALTQTQAVEGEIDLAKLKKFIAYCRVKCGPRLSAEAAEKLKNRYIIMRSGARQHERDS
  DRRSSIPITVRQLEAIVRIAEALSKMKLQPFATEADVEEALRLFQVSTLDAALSGTLSGV
  EGFTSQEDQEMLSRIEKQLKRRFAIGSQVSEHSIIKDFTKQKYPEHAIHKVLQLMLRRGE
  IQHRMQRKVLYRLK
• Function: Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.
• KEGG Pathway:
  D. replication (hsa03030)
  Cell cycle (hsa04110)
• Reactome Pathway:
  Unwinding of DNA (R-HSA-176974)
  Assembly of the pre-replicative complex (R-HSA-68867)
  Orc1 removal from chromatin (R-HSA-68949)
  Activation of the pre-replicative complex (R-HSA-68962)
  Switching of origins to a post-replicative state (R-HSA-69052)
  Activation of ATR in response to replication stress (R-HSA-176187)

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Definitive	Biomarker	[1]
Bladder transitional cell carcinoma	DISNL46A	Definitive	Altered Expression	[2]
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[3]
Carcinoma of esophagus	DISS6G4D	Definitive	Altered Expression	[4]
Dyspepsia	DISYEEY6	Definitive	Altered Expression	[4]
Esophageal cancer	DISGB2VN	Definitive	Altered Expression	[4]
Neoplasm	DISZKGEW	Definitive	Biomarker	[5]
Urinary bladder cancer	DISDV4T7	Definitive	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[7]
Alcohol use disorder	DISMB65Y	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[9]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[9]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Biomarker	[10]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[11]
Dysplasia of cervix	DISOAROS	Strong	Biomarker	[10]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Altered Expression	[6]
Gastric adenocarcinoma	DISWWLTC	Strong	Altered Expression	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[14]
Meier-Gorlin syndrome	DISCFIU3	Strong	Biomarker	[15]
Prostate cancer	DISF190Y	Strong	Altered Expression	[16]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[16]
Skin disease	DISDW8R6	Strong	Altered Expression	[17]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[18]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Biomarker	[18]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[19]
Meningioma	DISPT4TG	moderate	Biomarker	[20]
Mungan syndrome	DISNR0AY	moderate	Genetic Variation	[21]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[19]
Desmoid tumour	DISGX357	Limited	Altered Expression	[22]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[23]
Meier-Gorlin syndrome 8	DISAX05K	Limited	Unknown	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of DNA replication licensing factor MCM5 (MCM5).	[25]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[26]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA replication licensing factor MCM5 (MCM5).	[29]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DNA replication licensing factor MCM5 (MCM5).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[31]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[34]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of DNA replication licensing factor MCM5 (MCM5).	[35]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[36]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[36]
Selenium	DM25CGV	Approved	Selenium increases the expression of DNA replication licensing factor MCM5 (MCM5).	[38]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DNA replication licensing factor MCM5 (MCM5).	[39]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[40]
Menadione	DMSJDTY	Approved	Menadione affects the expression of DNA replication licensing factor MCM5 (MCM5).	[41]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[42]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[43]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[44]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[45]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of DNA replication licensing factor MCM5 (MCM5).	[46]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[47]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[48]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[50]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[52]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[53]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[54]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[56]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[57]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA replication licensing factor MCM5 (MCM5).	[59]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[60]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[61]
Manganese	DMKT129	Investigative	Manganese decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[62]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[63]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of DNA replication licensing factor MCM5 (MCM5).	[64]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of DNA replication licensing factor MCM5 (MCM5).	[32]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of DNA replication licensing factor MCM5 (MCM5).	[37]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of DNA replication licensing factor MCM5 (MCM5).	[58]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of DNA replication licensing factor MCM5 (MCM5).	[49]

References

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