Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX4HD45)

• DOT Name: Cyclin-A1 (CCNA1)
• Gene Name: CCNA1
• Related Disease:
  Advanced cancer
  Atrichia with papular lesions
  Azoospermia
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cervical Intraepithelial neoplasia
  Childhood acute lymphoblastic leukemia
  Colorectal carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Glioma
  Head-neck squamous cell carcinoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Human papillomavirus infection
  leukaemia
  Leukemia
  Liver cirrhosis
  Lung cancer
  Male infertility
  Oligospermia
  Ovarian cancer
  Ovarian neoplasm
  Precancerous condition
  Promyelocytic leukaemia
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Retinoblastoma
  Testicular cancer
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Urinary bladder neoplasm
  Vulvar squamous intraepithelial lesion
  Acute myelogenous leukaemia
  Laryngeal squamous cell carcinoma
  Lung carcinoma
  Acute lymphocytic leukaemia
  Breast cancer
  Cervical cancer
  Cervical carcinoma
  facioscapulohumeral muscular dystrophy
  Plasma cell myeloma
  Thyroid gland papillary carcinoma
  Wilms tumor
• UniProt ID: CCNA1_HUMAN
• Pfam ID: PF02984 ; PF00134 ; PF16500
• Sequence:
  METGFPAIMYPGSFIGGWGEEYLSWEGPGLPDFVFQQQPVESEAMHCSNPKSGVVLATVA
  RGPDACQILTRAPLGQDPPQRTVLGLLTANGQYRRTCGQGITRIRCYSGSENAFPPAGKK
  ALPDCGVQEPPKQGFDIYMDELEQGDRDSCSVREGMAFEDVYEVDTGTLKSDLHFLLDFN
  TVSPMLVDSSLLSQSEDISSLGTDVINVTEYAEEIYQYLREAEIRHRPKAHYMKKQPDIT
  EGMRTILVDWLVEVGEEYKLRAETLYLAVNFLDRFLSCMSVLRGKLQLVGTAAMLLASKY
  EEIYPPEVDEFVYITDDTYTKRQLLKMEHLLLKVLAFDLTVPTTNQFLLQYLRRQGVCVR
  TENLAKYVAELSLLEADPFLKYLPSLIAAAAFCLANYTVNKHFWPETLAAFTGYSLSEIV
  PCLSELHKAYLDIPHRPQQAIREKYKASKYLCVSLMEPPAVLLLQ
• Function: May be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions. May primarily function in the control of the germline meiotic cell cycle and additionally in the control of mitotic cell cycle in some somatic cells.
• Tissue Specificity: Very high levels in testis and very low levels in brain. Also found in myeloid leukemia cell lines.
• KEGG Pathway:
  Cell cycle (hsa04110)
  AMPK sig.ling pathway (hsa04152)
  Cellular senescence (hsa04218)
  Progesterone-mediated oocyte maturation (hsa04914)
  Hepatitis B (hsa05161)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Viral carcinogenesis (hsa05203)
  Acute myeloid leukemia (hsa05221)
• Reactome Pathway:
  Phosphorylation of proteins involved in the G2/M transition by Cyclin A (R-HSA-170145)
  Telomere Extension By Telomerase (R-HSA-171319)
  Cdc20 (R-HSA-174184)
  Regulation of APC/C activators between G1/S and early anaphase (R-HSA-176408)
  SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586)
  Ub-specific processing proteases (R-HSA-5689880)
  Processing of DNA double-strand break ends (R-HSA-5693607)
  TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest (R-HSA-6804116)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  Regulation of TP53 Degradation (R-HSA-6804757)
  G2 Phase (R-HSA-68911)
  Orc1 removal from chromatin (R-HSA-68949)
  CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin A/B1/B2 associated events during G2/M transition (R-HSA-69273)
  p53-Dependent G1 DNA Damage Response (R-HSA-69563)
  Cyclin A (R-HSA-69656)
  G0 and Early G1 (R-HSA-1538133)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Atrichia with papular lesions	DIS80CUB	Strong	Altered Expression	[2]
Azoospermia	DIS94181	Strong	Genetic Variation	[3]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Posttranslational Modification	[8]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[11]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[13]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[14]
Human papillomavirus infection	DISX61LX	Strong	Biomarker	[15]
leukaemia	DISS7D1V	Strong	Altered Expression	[2]
Leukemia	DISNAKFL	Strong	Altered Expression	[2]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[16]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[3]
Oligospermia	DIS6YJF3	Strong	Posttranslational Modification	[18]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Precancerous condition	DISV06FL	Strong	Posttranslational Modification	[19]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[20]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[20]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[21]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[22]
Testicular cancer	DIS6HNYO	Strong	Altered Expression	[23]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Biomarker	[24]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[25]
Vulvar squamous intraepithelial lesion	DISULIZR	Strong	Posttranslational Modification	[26]
Acute myelogenous leukaemia	DISCSPTN	moderate	Altered Expression	[27]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Altered Expression	[28]
Lung carcinoma	DISTR26C	moderate	Biomarker	[29]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Genetic Variation	[30]
Breast cancer	DIS7DPX1	Limited	Biomarker	[5]
Cervical cancer	DISFSHPF	Limited	Biomarker	[31]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[31]
facioscapulohumeral muscular dystrophy	DISSE0H0	Limited	Altered Expression	[32]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[33]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Altered Expression	[34]
Wilms tumor	DISB6T16	Limited	Biomarker	[35]

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 Cyclin-A1 (CCNA1).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cyclin-A1 (CCNA1).	[54]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cyclin-A1 (CCNA1).	[59]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Cyclin-A1 (CCNA1).	[63]

29 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 Cyclin-A1 (CCNA1).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cyclin-A1 (CCNA1).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cyclin-A1 (CCNA1).	[39]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclin-A1 (CCNA1).	[40]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Cyclin-A1 (CCNA1).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cyclin-A1 (CCNA1).	[42]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Cyclin-A1 (CCNA1).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cyclin-A1 (CCNA1).	[38]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cyclin-A1 (CCNA1).	[43]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Cyclin-A1 (CCNA1).	[44]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Cyclin-A1 (CCNA1).	[45]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Cyclin-A1 (CCNA1).	[46]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Cyclin-A1 (CCNA1).	[47]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Cyclin-A1 (CCNA1).	[48]
Atropine	DMEN6X7	Approved	Atropine increases the expression of Cyclin-A1 (CCNA1).	[49]
Silymarin	DMXBYQR	Phase 4	Silymarin decreases the expression of Cyclin-A1 (CCNA1).	[50]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cyclin-A1 (CCNA1).	[51]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Cyclin-A1 (CCNA1).	[52]
Triptolide	DMCMDVR	Phase 3	Triptolide decreases the expression of Cyclin-A1 (CCNA1).	[53]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Cyclin-A1 (CCNA1).	[51]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cyclin-A1 (CCNA1).	[55]
Harmine	DMPA5WD	Patented	Harmine increases the expression of Cyclin-A1 (CCNA1).	[56]
Taxifolin	DMQJSF9	Preclinical	Taxifolin decreases the expression of Cyclin-A1 (CCNA1).	[57]
EHT-1864	DMYAMP5	Terminated	EHT-1864 decreases the expression of Cyclin-A1 (CCNA1).	[58]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cyclin-A1 (CCNA1).	[47]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Cyclin-A1 (CCNA1).	[60]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Cyclin-A1 (CCNA1).	[61]
Okadaic acid	DM47CO1	Investigative	Okadaic acid affects the expression of Cyclin-A1 (CCNA1).	[62]
tryptanthrin	DMTRYCI	Investigative	tryptanthrin decreases the expression of Cyclin-A1 (CCNA1).	[64]

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