Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVY53VG)

• DOT Name: DNA replication factor Cdt1 (CDT1)
• Synonyms: Double parked homolog; DUP
• Gene Name: CDT1
• Related Disease:
  B-cell neoplasm
  Hepatocellular carcinoma
  Meier-Gorlin syndrome 4
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Campylobacteriosis
  Chromosomal disorder
  Isolated growth hormone deficiency type IA
  Lymphoblastic lymphoma
  Mantle cell lymphoma
  Myeloproliferative neoplasm
  Pelizeaus-Merzbacher spectrum disorder
  Prostate carcinoma
  Retinoblastoma
  Seckel syndrome
  Syndromic X-linked intellectual disability Lubs type
  Meier-Gorlin syndrome
  Melanoma
  Neoplasm
  Psychotic disorder
  Pulmonary emphysema
• UniProt ID: CDT1_HUMAN
• PDB ID: 2LE8; 2WVR; 6QCG
• Pfam ID: PF08839 ; PF16679
• Sequence:
  MEQRRVTDFFARRRPGPPRIAPPKLACRTPSPARPALRAPASATSGSRKRARPPAAPGRD
  QARPPARRRLRLSVDEVSSPSTPEAPDIPACPSPGQKIKKSTPAAGQPPHLTSAQDQDTI
  SELASCLQRARELGARVRALKASAQDAGESCTPEAEGRPEEPCGEKAPAYQRFHALAQPG
  LPGLVLPYKYQVLAEMFRSMDTIVGMLHNRSETPTFAKVQRGVQDMMRRRFEECNVGQIK
  TVYPASYRFRQERSVPTFKDGTRRSDYQLTIEPLLEQEADGAAPQLTASRLLQRRQIFSQ
  KLVEHVKEHHKAFLASLSPAMVVPEDQLTRWHPRFNVDEVPDIEPAALPQPPATEKLTTA
  QEVLARARNLISPRMEKALSQLALRSAAPSSPGSPRPALPATPPATPPAASPSALKGVSQ
  DLLERIRAKEAQKQLAQMTRCPEQEQRLQRLERLPELARVLRSVFVSERKPALSMEVACA
  RMVGSCCTIMSPGEMEKHLLLLSELLPDWLSLHRIRTDTYVKLDKAADLAHITARLAHQT
  RAEEGL
• Function: Required for both DNA replication and mitosis. DNA replication licensing factor, required for pre-replication complex assembly. Cooperates with CDC6 and the origin recognition complex (ORC) during G1 phase of the cell cycle to promote the loading of the mini-chromosome maintenance (MCM) complex onto DNA to generate pre-replication complexes (pre-RC). Required also for mitosis by promoting stable kinetochore-microtubule attachments. Potential oncogene.
• KEGG Pathway: Cell cycle (hsa04110)
• Reactome Pathway:
  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)
  G1/S-Specific Transcription (R-HSA-69205)
  Assembly of the pre-replicative complex (R-HSA-68867)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[2]
Meier-Gorlin syndrome 4	DIS8W3JZ	Definitive	Autosomal recessive	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[6]
Campylobacteriosis	DISF18CN	Strong	Biomarker	[7]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[8]
Isolated growth hormone deficiency type IA	DISLPIAM	Strong	Genetic Variation	[9]
Lymphoblastic lymphoma	DISB9ZYC	Strong	Biomarker	[8]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[10]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Biomarker	[11]
Pelizeaus-Merzbacher spectrum disorder	DIS1ODJO	Strong	Genetic Variation	[12]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[13]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[14]
Seckel syndrome	DISEVUBA	Strong	Biomarker	[11]
Syndromic X-linked intellectual disability Lubs type	DISJ54F6	Strong	Genetic Variation	[12]
Meier-Gorlin syndrome	DISCFIU3	Supportive	Autosomal dominant	[15]
Melanoma	DIS1RRCY	Limited	Biomarker	[16]
Neoplasm	DISZKGEW	Limited	Biomarker	[17]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[18]
Pulmonary emphysema	DIS5M7HZ	Limited	Genetic Variation	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of DNA replication factor Cdt1 (CDT1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of DNA replication factor Cdt1 (CDT1).	[41]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of DNA replication factor Cdt1 (CDT1).	[42]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of DNA replication factor Cdt1 (CDT1).	[44]

28 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 factor Cdt1 (CDT1).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA replication factor Cdt1 (CDT1).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA replication factor Cdt1 (CDT1).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA replication factor Cdt1 (CDT1).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of DNA replication factor Cdt1 (CDT1).	[25]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DNA replication factor Cdt1 (CDT1).	[26]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of DNA replication factor Cdt1 (CDT1).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA replication factor Cdt1 (CDT1).	[28]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA replication factor Cdt1 (CDT1).	[28]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of DNA replication factor Cdt1 (CDT1).	[29]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of DNA replication factor Cdt1 (CDT1).	[30]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of DNA replication factor Cdt1 (CDT1).	[31]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of DNA replication factor Cdt1 (CDT1).	[32]
Menadione	DMSJDTY	Approved	Menadione affects the expression of DNA replication factor Cdt1 (CDT1).	[33]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of DNA replication factor Cdt1 (CDT1).	[34]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of DNA replication factor Cdt1 (CDT1).	[35]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of DNA replication factor Cdt1 (CDT1).	[36]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of DNA replication factor Cdt1 (CDT1).	[37]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of DNA replication factor Cdt1 (CDT1).	[30]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of DNA replication factor Cdt1 (CDT1).	[38]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of DNA replication factor Cdt1 (CDT1).	[39]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of DNA replication factor Cdt1 (CDT1).	[26]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of DNA replication factor Cdt1 (CDT1).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of DNA replication factor Cdt1 (CDT1).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA replication factor Cdt1 (CDT1).	[45]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of DNA replication factor Cdt1 (CDT1).	[46]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of DNA replication factor Cdt1 (CDT1).	[47]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of DNA replication factor Cdt1 (CDT1).	[48]

References

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