Details of Drug Off-Target (DOT)

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

• DOT Name: DNA replication licensing factor MCM2 (MCM2)
• Synonyms: EC 3.6.4.12; Minichromosome maintenance protein 2 homolog; Nuclear protein BM28
• Gene Name: MCM2
• Related Disease:
  Meningioma
  Acute lymphocytic leukaemia
  Adenoma
  Alzheimer disease
  Autosomal dominant nonsyndromic hearing loss 70
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Childhood acute lymphoblastic leukemia
  Colon carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Liver cirrhosis
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Myelodysplastic syndrome
  Neoplasm
  Non-small-cell lung cancer
  Polycystic ovarian syndrome
  Retinoblastoma
  Sarcoma
  Squamous cell carcinoma
  Stomach cancer
  Urinary bladder neoplasm
  Clear cell renal carcinoma
  Colonic neoplasm
  Lymphoma
  Melanoma
  Renal cell carcinoma
  Autosomal dominant nonsyndromic hearing loss
  Adenocarcinoma
  Advanced cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colorectal neoplasm
  Hepatitis C virus infection
  Matthew-Wood syndrome
  Nonsyndromic genetic hearing loss
  Osteosarcoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: MCM2_HUMAN
• PDB ID: 4UUZ; 5BNV; 5BNX; 5BO0; 5C3I; 5JA4; 6XTX; 6XTY; 6YA7; 7CIZ; 7CJ0; 7PFO; 7PLO; 7W1Y; 7W68; 8B9D
• EC Number: 3.6.4.12
• Pfam ID: PF00493 ; PF12619 ; PF17855 ; PF14551 ; PF17207
• Sequence:
  MAESSESFTMASSPAQRRRGNDPLTSSPGRSSRRTDALTSSPGRDLPPFEDESEGLLGTE
  GPLEEEEDGEELIGDGMERDYRAIPELDAYEAEGLALDDEDVEELTASQREAAERAMRQR
  DREAGRGLGRMRRGLLYDSDEEDEERPARKRRQVERATEDGEEDEEMIESIENLEDLKGH
  SVREWVSMAGPRLEIHHRFKNFLRTHVDSHGHNVFKERISDMCKENRESLVVNYEDLAAR
  EHVLAYFLPEAPAELLQIFDEAALEVVLAMYPKYDRITNHIHVRISHLPLVEELRSLRQL
  HLNQLIRTSGVVTSCTGVLPQLSMVKYNCNKCNFVLGPFCQSQNQEVKPGSCPECQSAGP
  FEVNMEETIYQNYQRIRIQESPGKVAAGRLPRSKDAILLADLVDSCKPGDEIELTGIYHN
  NYDGSLNTANGFPVFATVILANHVAKKDNKVAVGELTDEDVKMITSLSKDQQIGEKIFAS
  IAPSIYGHEDIKRGLALALFGGEPKNPGGKHKVRGDINVLLCGDPGTAKSQFLKYIEKVS
  SRAIFTTGQGASAVGLTAYVQRHPVSREWTLEAGALVLADRGVCLIDEFDKMNDQDRTSI
  HEAMEQQSISISKAGIVTSLQARCTVIAAANPIGGRYDPSLTFSENVDLTEPIISRFDIL
  CVVRDTVDPVQDEMLARFVVGSHVRHHPSNKEEEGLANGSAAEPAMPNTYGVEPLPQEVL
  KKYIIYAKERVHPKLNQMDQDKVAKMYSDLRKESMATGSIPITVRHIESMIRMAEAHARI
  HLRDYVIEDDVNMAIRVMLESFIDTQKFSVMRSMRKTFARYLSFRRDNNELLLFILKQLV
  AEQVTYQRNRFGAQQDTIEVPEKDLVDKARQINIHNLSAFYDSELFRMNKFSHDLKRKMI
  LQQF
• 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. Required for the entry in S phase and for cell division. Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis.
• 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

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Meningioma	DISPT4TG	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[2]
Adenoma	DIS78ZEV	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Autosomal dominant nonsyndromic hearing loss 70	DIS97336	Strong	Autosomal dominant	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[7]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[7]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Altered Expression	[14]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[14]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[15]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[16]
Neoplasm	DISZKGEW	Strong	Altered Expression	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[18]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[19]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[18]
Sarcoma	DISZDG3U	Strong	Altered Expression	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[17]
Stomach cancer	DISKIJSX	Strong	Biomarker	[21]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[22]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[23]
Colonic neoplasm	DISSZ04P	moderate	Therapeutic	[24]
Lymphoma	DISN6V4S	moderate	Altered Expression	[25]
Melanoma	DIS1RRCY	moderate	Biomarker	[26]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[23]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[5]
Adenocarcinoma	DIS3IHTY	Disputed	Altered Expression	[27]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[28]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[29]
Breast cancer	DIS7DPX1	Limited	Biomarker	[30]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[30]
Colon cancer	DISVC52G	Limited	Altered Expression	[8]
Colorectal neoplasm	DISR1UCN	Limited	Biomarker	[27]
Hepatitis C virus infection	DISQ0M8R	Limited	Altered Expression	[31]
Matthew-Wood syndrome	DISA7HR7	Limited	Altered Expression	[32]
Nonsyndromic genetic hearing loss	DISZX61P	Limited	Autosomal dominant	[33]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[29]
Prostate cancer	DISF190Y	Limited	Biomarker	[34]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	DNA replication licensing factor MCM2 (MCM2) affects the response to substance of Fluorouracil.	[73]

39 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 DNA replication licensing factor MCM2 (MCM2).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[39]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DNA replication licensing factor MCM2 (MCM2).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DNA replication licensing factor MCM2 (MCM2).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[44]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[44]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[45]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DNA replication licensing factor MCM2 (MCM2).	[46]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[47]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[48]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[49]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[50]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[51]
Malathion	DMXZ84M	Approved	Malathion increases the expression of DNA replication licensing factor MCM2 (MCM2).	[52]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[53]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[54]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of DNA replication licensing factor MCM2 (MCM2).	[40]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[56]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[57]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[51]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[59]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[61]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[63]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[64]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[24]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA replication licensing factor MCM2 (MCM2).	[66]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[67]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[68]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[69]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[70]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of DNA replication licensing factor MCM2 (MCM2).	[51]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of DNA replication licensing factor MCM2 (MCM2).	[71]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of DNA replication licensing factor MCM2 (MCM2).	[72]
Chlorphrifos oxon	DMGBT68	Investigative	Chlorphrifos oxon increases the expression of DNA replication licensing factor MCM2 (MCM2).	[71]

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 MCM2 (MCM2).	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
G1	DMTV42K	Phase 1/2	G1 increases the phosphorylation of DNA replication licensing factor MCM2 (MCM2).	[58]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of DNA replication licensing factor MCM2 (MCM2).	[60]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of DNA replication licensing factor MCM2 (MCM2).	[62]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of DNA replication licensing factor MCM2 (MCM2).	[62]

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