Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDULQF9)

• DOT Name: G1/S-specific cyclin-D2 (CCND2)
• Gene Name: CCND2
• Related Disease:
  Lung cancer
  Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
  Advanced cancer
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Colon cancer
  Colonic neoplasm
  Colorectal adenocarcinoma
  Colorectal adenoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Erectile dysfunction
  Glaucoma/ocular hypertension
  Hepatocellular carcinoma
  Hydrocephalus
  Lung neoplasm
  Mantle cell lymphoma
  Megalencephaly
  Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3
  Myocardial ischemia
  Nephritis
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Plasma cell myeloma
  Polydactyly
  Schizophrenia
  Transitional cell carcinoma
  Colorectal neoplasm
  Movement disorder
  Non-insulin dependent diabetes
  Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
  Acute myelogenous leukaemia
  Bilateral perisylvian polymicrogyria
  Colorectal carcinoma
  Communicating hydrocephalus
  Congenital hydrocephalus
  Gastric cancer
  Polydactyly, postaxial, type A1
  Postaxial polydactyly
  Postaxial polydactyly type A
  Prostate neoplasm
• UniProt ID: CCND2_HUMAN
• PDB ID: 6EI2
• Pfam ID: PF02984 ; PF00134
• Sequence:
  MELLCHEVDPVRRAVRDRNLLRDDRVLQNLLTIEERYLPQCSYFKCVQKDIQPYMRRMVA
  TWMLEVCEEQKCEEEVFPLAMNYLDRFLAGVPTPKSHLQLLGAVCMFLASKLKETSPLTA
  EKLCIYTDNSIKPQELLEWELVVLGKLKWNLAAVTPHDFIEHILRKLPQQREKLSLIRKH
  AQTFIALCATDFKFAMYPPSMIATGSVGAAICGLQQDEEVSSLTCDALTELLAKITNTDV
  DCLKACQEQIEAVLLNSLQQYRQDQRDGSKSEDELDQASTPTDVRDIDL
• Function: Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals.
• KEGG Pathway:
  FoxO sig.ling pathway (hsa04068)
  Cell cycle (hsa04110)
  p53 sig.ling pathway (hsa04115)
  PI3K-Akt sig.ling pathway (hsa04151)
  Cellular senescence (hsa04218)
  Wnt sig.ling pathway (hsa04310)
  Hedgehog sig.ling pathway (hsa04340)
  Hippo sig.ling pathway (hsa04390)
  Focal adhesion (hsa04510)
  JAK-STAT sig.ling pathway (hsa04630)
  Prolactin sig.ling pathway (hsa04917)
  Measles (hsa05162)
  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)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  Regulation of RUNX1 Expression and Activity (R-HSA-8934593)
  Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069)
  Drug-mediated inhibition of CDK4/CDK6 activity (R-HSA-9754119)
  Cyclin D associated events in G1 (R-HSA-69231)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Posttranslational Modification	[1]
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1	DIS06C5U	Definitive	Autosomal dominant	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[6]
Colon cancer	DISVC52G	Strong	Genetic Variation	[7]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[8]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[7]
Colorectal adenoma	DISTSVHM	Strong	Genetic Variation	[9]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[7]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[7]
Erectile dysfunction	DISD8MTH	Strong	Biomarker	[10]
Glaucoma/ocular hypertension	DISLBXBY	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[13]
Lung neoplasm	DISVARNB	Strong	Posttranslational Modification	[14]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[15]
Megalencephaly	DISYW5SV	Strong	Biomarker	[13]
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3	DIS94HL6	Strong	Autosomal dominant	[16]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[17]
Nephritis	DISQZQ70	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[20]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[20]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[21]
Polydactyly	DIS25BMZ	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[22]
Transitional cell carcinoma	DISWVVDR	Strong	Biomarker	[23]
Colorectal neoplasm	DISR1UCN	moderate	Genetic Variation	[7]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[24]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Genetic Variation	[6]
Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome	DISWVM8Y	Supportive	Autosomal dominant	[2]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Genetic Variation	[25]
Bilateral perisylvian polymicrogyria	DISIF9XK	Limited	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[7]
Communicating hydrocephalus	DIS33112	Limited	Biomarker	[13]
Congenital hydrocephalus	DIS7O6UL	Limited	Biomarker	[13]
Gastric cancer	DISXGOUK	Limited	Biomarker	[3]
Polydactyly, postaxial, type A1	DISFMXAM	Limited	Biomarker	[13]
Postaxial polydactyly	DIS085OV	Limited	Biomarker	[13]
Postaxial polydactyly type A	DIS4IIPW	Limited	Biomarker	[13]
Prostate neoplasm	DISHDKGQ	Limited	Altered Expression	[26]

66 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[27]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of G1/S-specific cyclin-D2 (CCND2).	[29]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[31]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[32]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of G1/S-specific cyclin-D2 (CCND2).	[33]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of G1/S-specific cyclin-D2 (CCND2).	[34]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[35]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of G1/S-specific cyclin-D2 (CCND2).	[36]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[37]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[38]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of G1/S-specific cyclin-D2 (CCND2).	[39]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of G1/S-specific cyclin-D2 (CCND2).	[40]
Selenium	DM25CGV	Approved	Selenium decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[41]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of G1/S-specific cyclin-D2 (CCND2).	[42]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of G1/S-specific cyclin-D2 (CCND2).	[43]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[44]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[45]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[46]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[47]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[48]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[49]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[50]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[44]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of G1/S-specific cyclin-D2 (CCND2).	[51]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[53]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of G1/S-specific cyclin-D2 (CCND2).	[54]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[55]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[56]
Clofibrate	DMPC1J7	Approved	Clofibrate decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[47]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[57]
Lamivudine	DMI347A	Approved	Lamivudine decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[53]
Letrozole	DMH07Y3	Approved	Letrozole decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[58]
Ciprofibrate	DMGC5DB	Approved	Ciprofibrate decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[47]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[59]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[60]
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[61]
MLN4924	DMP36KD	Phase 3	MLN4924 affects the expression of G1/S-specific cyclin-D2 (CCND2).	[62]
Peretinoin	DMESAZK	Phase 3	Peretinoin decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[63]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of G1/S-specific cyclin-D2 (CCND2).	[33]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[64]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of G1/S-specific cyclin-D2 (CCND2).	[65]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[66]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[68]
LY294002	DMY1AFS	Phase 1	LY294002 increases the expression of G1/S-specific cyclin-D2 (CCND2).	[69]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of G1/S-specific cyclin-D2 (CCND2).	[70]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[44]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of G1/S-specific cyclin-D2 (CCND2).	[71]
SK-7041	DM7DNOG	Preclinical	SK-7041 increases the expression of G1/S-specific cyclin-D2 (CCND2).	[72]
Wortmannin	DM8EVK5	Terminated	Wortmannin increases the expression of G1/S-specific cyclin-D2 (CCND2).	[69]
Calphostin C	DM9X2D0	Terminated	Calphostin C decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[73]
Acteoside	DM0YHKB	Terminated	Acteoside decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[74]
AG490	DM3WKO5	Terminated	AG490 decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[64]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[66]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[76]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[77]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of G1/S-specific cyclin-D2 (CCND2).	[78]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[79]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[80]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[81]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[82]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the expression of G1/S-specific cyclin-D2 (CCND2).	[83]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[47]
ANTHRAQUINONE	DM29I0Y	Investigative	ANTHRAQUINONE decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[84]
3-acetyl-11-keto-beta-boswellic acid	DMGO2D7	Investigative	3-acetyl-11-keto-beta-boswellic acid decreases the expression of G1/S-specific cyclin-D2 (CCND2).	[85]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Azacitidine	DMTA5OE	Approved	Azacitidine affects the methylation of G1/S-specific cyclin-D2 (CCND2).	[52]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of G1/S-specific cyclin-D2 (CCND2).	[67]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of G1/S-specific cyclin-D2 (CCND2).	[75]

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