Details of Drug Off-Target (DOT)

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

• DOT Name: DNA replication licensing factor MCM3 (MCM3)
• Synonyms: EC 3.6.4.12; DNA polymerase alpha holoenzyme-associated protein P1; P1-MCM3; RLF subunit beta; p102
• Gene Name: MCM3
• Related Disease:
  B-cell neoplasm
  Arteriosclerosis
  Atherosclerosis
  Autosomal recessive polycystic kidney disease
  Brain neoplasm
  Carcinoma
  Diabetic kidney disease
  Epithelial ovarian cancer
  Glioma
  Glomerulosclerosis
  Hepatitis C virus infection
  leukaemia
  Leukemia
  Malignant soft tissue neoplasm
  Medulloblastoma
  Melanoma
  Ovarian cancer
  Prostate cancer
  Prostate carcinoma
  Sarcoma
  Autoimmune disease
  Hepatocellular carcinoma
  Meningioma
  Adrenal adenoma
  Adrenocortical carcinoma
  Advanced cancer
  Clear cell renal carcinoma
  Cutaneous melanoma
  Renal cell carcinoma
  Squamous cell carcinoma
  Thyroid gland papillary carcinoma
• UniProt ID: MCM3_HUMAN
• PDB ID: 6XTX; 6XTY; 7PFO; 7PLO; 7W1Y; 7W68; 8B9D
• EC Number: 3.6.4.12
• Pfam ID: PF00493 ; PF17855 ; PF14551 ; PF17207
• Sequence:
  MAGTVVLDDVELREAQRDYLDFLDDEEDQGIYQSKVRELISDNQYRLIVNVNDLRRKNEK
  RANRLLNNAFEELVAFQRALKDFVASIDATYAKQYEEFYVGLEGSFGSKHVSPRTLTSCF
  LSCVVCVEGIVTKCSLVRPKVVRSVHYCPATKKTIERRYSDLTTLVAFPSSSVYPTKDEE
  NNPLETEYGLSVYKDHQTITIQEMPEKAPAGQLPRSVDVILDDDLVDKAKPGDRVQVVGT
  YRCLPGKKGGYTSGTFRTVLIACNVKQMSKDAQPSFSAEDIAKIKKFSKTRSKDIFDQLA
  KSLAPSIHGHDYVKKAILCLLLGGVERDLENGSHIRGDINILLIGDPSVAKSQLLRYVLC
  TAPRAIPTTGRGSSGVGLTAAVTTDQETGERRLEAGAMVLADRGVVCIDEFDKMSDMDRT
  AIHEVMEQGRVTIAKAGIHARLNARCSVLAAANPVYGRYDQYKTPMENIGLQDSLLSRFD
  LLFIMLDQMDPEQDREISDHVLRMHRYRAPGEQDGDAMPLGSAVDILATDDPNFSQEDQQ
  DTQIYEKHDNLLHGTKKKKEKMVSAAFMKKYIHVAKIIKPVLTQESATYIAEEYSRLRSQ
  DSMSSDTARTSPVTARTLETLIRLATAHAKARMSKTVDLQDAEEAVELVQYAYFKKVLEK
  EKKRKKRSEDESETEDEEEKSQEDQEQKRKRRKTRQPDAKDGDSYDPYDFSDTEEEMPQV
  HTPKTADSQETKESQKVELSESRLKAFKVALLDVFREAHAQSIGMNRLTESINRDSEEPF
  SSVEIQAALSKMQDDNQVMVSEGIIFLI
• 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 (Probable).
• 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

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[2]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[2]
Autosomal recessive polycystic kidney disease	DISPUS40	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[4]
Carcinoma	DISH9F1N	Strong	Altered Expression	[5]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Altered Expression	[8]
Glomerulosclerosis	DISJF20Z	Strong	Biomarker	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[9]
leukaemia	DISS7D1V	Strong	Altered Expression	[5]
Leukemia	DISNAKFL	Strong	Altered Expression	[5]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[10]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[11]
Melanoma	DIS1RRCY	Strong	Altered Expression	[5]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Altered Expression	[12]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[12]
Sarcoma	DISZDG3U	Strong	Biomarker	[10]
Autoimmune disease	DISORMTM	moderate	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[14]
Meningioma	DISPT4TG	moderate	Altered Expression	[15]
Adrenal adenoma	DISC2UN8	Limited	Biomarker	[16]
Adrenocortical carcinoma	DISZF4HX	Limited	Biomarker	[16]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[17]
Clear cell renal carcinoma	DISBXRFJ	Limited	Posttranslational Modification	[18]
Cutaneous melanoma	DIS3MMH9	Limited	Biomarker	[19]
Renal cell carcinoma	DISQZ2X8	Limited	Posttranslational Modification	[18]
Squamous cell carcinoma	DISQVIFL	Limited	Biomarker	[20]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Altered Expression	[21]

35 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 MCM3 (MCM3).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA replication licensing factor MCM3 (MCM3).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA replication licensing factor MCM3 (MCM3).	[26]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DNA replication licensing factor MCM3 (MCM3).	[27]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[28]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[29]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of DNA replication licensing factor MCM3 (MCM3).	[30]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[31]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[31]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DNA replication licensing factor MCM3 (MCM3).	[32]
Marinol	DM70IK5	Approved	Marinol decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[33]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DNA replication licensing factor MCM3 (MCM3).	[34]
Menadione	DMSJDTY	Approved	Menadione affects the expression of DNA replication licensing factor MCM3 (MCM3).	[35]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[36]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[37]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[38]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[39]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[40]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[41]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[42]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[43]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[49]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[44]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA replication licensing factor MCM3 (MCM3).	[27]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[52]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[53]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[54]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of DNA replication licensing factor MCM3 (MCM3).	[55]

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 MCM3 (MCM3).	[45]

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 replication licensing factor MCM3 (MCM3).	[48]

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