Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6NNLOD)

• DOT Name: Cell division control protein 45 homolog (CDC45)
• Synonyms: PORC-PI-1
• Gene Name: CDC45
• Related Disease:
  Hepatocellular carcinoma
  Meier-Gorlin syndrome 7
  Craniosynostosis
  Glioma
  Lung cancer
  Lung carcinoma
  Megalencephaly-capillary malformation-polymicrogyria syndrome
  Neoplasm
  Non-small-cell lung cancer
  Rothmund-Thomson syndrome
  Colorectal carcinoma
  DiGeorge syndrome
  Mungan syndrome
  Shprintzen-Goldberg syndrome
  Meier-Gorlin syndrome
  Metastatic malignant neoplasm
  Thyroid gland papillary carcinoma
• UniProt ID: CDC45_HUMAN
• PDB ID: 5DGO; 6XTX; 6XTY; 7PFO; 7PLO
• Pfam ID: PF02724
• Sequence:
  MFVSDFRKEFYEVVQSQRVLLFVASDVDALCACKILQALFQCDHVQYTLVPVSGWQELET
  AFLEHKEQFHYFILINCGANVDLLDILQPDEDTIFFVCDTHRPVNVVNVYNDTQIKLLIK
  QDDDLEVPAYEDIFRDEEEDEEHSGNDSDGSEPSEKRTRLEEEIVEQTMRRRQRREWEAR
  RRDILFDYEQYEYHGTSSAMVMFELAWMLSKDLNDMLWWAIVGLTDQWVQDKITQMKYVT
  DVGVLQRHVSRHNHRNEDEENTLSVDCTRISFEYDLRLVLYQHWSLHDSLCNTSYTAARF
  KLWSVHGQKRLQEFLADMGLPLKQVKQKFQAMDISLKENLREMIEESANKFGMKDMRVQT
  FSIHFGFKHKFLASDVVFATMSLMESPEKDGSGTDHFIQALDSLSRSNLDKLYHGLELAK
  KQLRATQQTIASCLCTNLVISQGPFLYCSLMEGTPDVMLFSRPASLSLLSKHLLKSFVCS
  TKNRRCKLLPLVMAAPLSMEHGTVTVVGIPPETDSSDRKNFFGRAFEKAAESTSSRMLHN
  HFDLSVIELKAEDRSKFLDALISLLS
• Function: Required for initiation of chromosomal DNA replication. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built.
• Tissue Specificity: Widely expressed, highest levels are found in adult testis and thymus and in fetal liver.
• KEGG Pathway: Cell cycle (hsa04110)
• Reactome Pathway:
  Unwinding of DNA (R-HSA-176974)
  Activation of the pre-replicative complex (R-HSA-68962)
  G1/S-Specific Transcription (R-HSA-69205)
  Activation of ATR in response to replication stress (R-HSA-176187)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Meier-Gorlin syndrome 7	DISX4K0R	Definitive	Autosomal recessive	[2]
Craniosynostosis	DIS6J405	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[5]
Lung carcinoma	DISTR26C	Strong	Biomarker	[5]
Megalencephaly-capillary malformation-polymicrogyria syndrome	DISAHLVO	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[7]
Rothmund-Thomson syndrome	DISGVBCV	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[9]
DiGeorge syndrome	DIST1RKO	moderate	Biomarker	[10]
Mungan syndrome	DISNR0AY	moderate	Biomarker	[11]
Shprintzen-Goldberg syndrome	DISQH6P3	moderate	Biomarker	[10]
Meier-Gorlin syndrome	DISCFIU3	Supportive	Autosomal dominant	[12]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Biomarker	[13]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[14]

43 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 Cell division control protein 45 homolog (CDC45).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cell division control protein 45 homolog (CDC45).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cell division control protein 45 homolog (CDC45).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cell division control protein 45 homolog (CDC45).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cell division control protein 45 homolog (CDC45).	[19]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cell division control protein 45 homolog (CDC45).	[20]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cell division control protein 45 homolog (CDC45).	[21]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cell division control protein 45 homolog (CDC45).	[22]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cell division control protein 45 homolog (CDC45).	[23]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cell division control protein 45 homolog (CDC45).	[23]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cell division control protein 45 homolog (CDC45).	[24]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cell division control protein 45 homolog (CDC45).	[25]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Cell division control protein 45 homolog (CDC45).	[26]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cell division control protein 45 homolog (CDC45).	[27]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cell division control protein 45 homolog (CDC45).	[28]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Cell division control protein 45 homolog (CDC45).	[29]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Cell division control protein 45 homolog (CDC45).	[30]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Cell division control protein 45 homolog (CDC45).	[31]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cell division control protein 45 homolog (CDC45).	[32]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Cell division control protein 45 homolog (CDC45).	[33]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Cell division control protein 45 homolog (CDC45).	[34]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Cell division control protein 45 homolog (CDC45).	[35]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Cell division control protein 45 homolog (CDC45).	[36]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Cell division control protein 45 homolog (CDC45).	[37]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Cell division control protein 45 homolog (CDC45).	[38]
Methamphetamine	DMPM4SK	Approved	Methamphetamine decreases the expression of Cell division control protein 45 homolog (CDC45).	[39]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Cell division control protein 45 homolog (CDC45).	[40]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cell division control protein 45 homolog (CDC45).	[41]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cell division control protein 45 homolog (CDC45).	[20]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Cell division control protein 45 homolog (CDC45).	[42]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Cell division control protein 45 homolog (CDC45).	[43]
Plevitrexed	DM7Y60I	Phase 2	Plevitrexed increases the expression of Cell division control protein 45 homolog (CDC45).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cell division control protein 45 homolog (CDC45).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cell division control protein 45 homolog (CDC45).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cell division control protein 45 homolog (CDC45).	[47]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cell division control protein 45 homolog (CDC45).	[48]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cell division control protein 45 homolog (CDC45).	[49]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Cell division control protein 45 homolog (CDC45).	[50]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Cell division control protein 45 homolog (CDC45).	[51]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Cell division control protein 45 homolog (CDC45).	[52]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Cell division control protein 45 homolog (CDC45).	[53]
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 Cell division control protein 45 homolog (CDC45).	[34]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of Cell division control protein 45 homolog (CDC45).	[54]

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 Cell division control protein 45 homolog (CDC45).	[46]

References

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