Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8HPTKJ)

• DOT Name: G1/S-specific cyclin-D1 (CCND1)
• Synonyms: B-cell lymphoma 1 protein; BCL-1; BCL-1 oncogene; PRAD1 oncogene
• Gene Name: CCND1
• UniProt ID: CCND1_HUMAN
• PDB ID: 2W96; 2W99; 2W9F; 2W9Z; 5VZU; 6P8E; 6P8F; 6P8G; 6P8H
• Pfam ID: PF02984 ; PF00134
• Sequence:
  MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETCAPSVSYFKCVQKEVLPSMRKIV
  ATWMLEVCEEQKCEEEVFPLAMNYLDRFLSLEPVKKSRLQLLGATCMFVASKMKETIPLT
  AEKLCIYTDNSIRPEELLQMELLLVNKLKWNLAAMTPHDFIEHFLSKMPEAEENKQIIRK
  HAQTFVALCATDVKFISNPPSMVAAGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCD
  PDCLRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDLACTPTDVRDVDI
• Function: Regulatory component of the cyclin D1-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. Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  FoxO sig.ling pathway (hsa04068)
  Cell cycle (hsa04110)
  p53 sig.ling pathway (hsa04115)
  PI3K-Akt sig.ling pathway (hsa04151)
  AMPK sig.ling pathway (hsa04152)
  Cellular senescence (hsa04218)
  Wnt sig.ling pathway (hsa04310)
  Hedgehog sig.ling pathway (hsa04340)
  Apelin sig.ling pathway (hsa04371)
  Hippo sig.ling pathway (hsa04390)
  Focal adhesion (hsa04510)
  Tight junction (hsa04530)
  JAK-STAT sig.ling pathway (hsa04630)
  Prolactin sig.ling pathway (hsa04917)
  Thyroid hormone sig.ling pathway (hsa04919)
  Oxytocin sig.ling pathway (hsa04921)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Cushing syndrome (hsa04934)
  Alcoholic liver disease (hsa04936)
  Hepatitis C (hsa05160)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Proteoglycans in cancer (hsa05205)
  MicroR.s in cancer (hsa05206)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Colorectal cancer (hsa05210)
  Pancreatic cancer (hsa05212)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Thyroid cancer (hsa05216)
  Melanoma (hsa05218)
  Bladder cancer (hsa05219)
  Chronic myeloid leukemia (hsa05220)
  Acute myeloid leukemia (hsa05221)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
  Viral myocarditis (hsa05416)
• Reactome Pathway:
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)
  RMTs methylate histone arginines (R-HSA-3214858)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Cyclin D associated events in G1 (R-HSA-69231)
  Ubiquitin-dependent degradation of Cyclin D (R-HSA-75815)
  PTK6 Regulates Cell Cycle (R-HSA-8849470)
  Transcriptional Regulation by VENTX (R-HSA-8853884)
  Transcriptional regulation by RUNX2 (R-HSA-8878166)
  Regulation of RUNX1 Expression and Activity (R-HSA-8934593)
  RUNX3 regulates WNT signaling (R-HSA-8951430)
  RUNX3 regulates p14-ARF (R-HSA-8951936)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638)
  Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069)
  Drug-mediated inhibition of CDK4/CDK6 activity (R-HSA-9754119)
  SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	G1/S-specific cyclin-D1 (CCND1) affects the response to substance of DTI-015.	[97]
Mitoxantrone	DMM39BF	Approved	G1/S-specific cyclin-D1 (CCND1) increases the Apoptosis ADR of Mitoxantrone.	[98]
Palbociclib	DMD7L94	Approved	G1/S-specific cyclin-D1 (CCND1) decreases the response to substance of Palbociclib.	[99]
Epanova	DMHEAGL	Approved	G1/S-specific cyclin-D1 (CCND1) affects the response to substance of Epanova.	[100]
ARZOXIFENE	DMOKCVI	Approved	G1/S-specific cyclin-D1 (CCND1) decreases the response to substance of ARZOXIFENE.	[101]
BMS-754807	DMPK32V	Phase 1	G1/S-specific cyclin-D1 (CCND1) increases the response to substance of BMS-754807.	[102]

1 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 G1/S-specific cyclin-D1 (CCND1).	[1]

99 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 G1/S-specific cyclin-D1 (CCND1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of G1/S-specific cyclin-D1 (CCND1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of G1/S-specific cyclin-D1 (CCND1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of G1/S-specific cyclin-D1 (CCND1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of G1/S-specific cyclin-D1 (CCND1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of G1/S-specific cyclin-D1 (CCND1).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[16]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of G1/S-specific cyclin-D1 (CCND1).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of G1/S-specific cyclin-D1 (CCND1).	[20]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[21]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[22]
Selenium	DM25CGV	Approved	Selenium increases the expression of G1/S-specific cyclin-D1 (CCND1).	[23]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[24]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[25]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[26]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[27]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[28]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[29]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[30]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[31]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[32]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[33]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of G1/S-specific cyclin-D1 (CCND1).	[34]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of G1/S-specific cyclin-D1 (CCND1).	[35]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[36]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of G1/S-specific cyclin-D1 (CCND1).	[37]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[38]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of G1/S-specific cyclin-D1 (CCND1).	[39]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[40]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of G1/S-specific cyclin-D1 (CCND1).	[41]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of G1/S-specific cyclin-D1 (CCND1).	[42]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of G1/S-specific cyclin-D1 (CCND1).	[43]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[44]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[38]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[45]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of G1/S-specific cyclin-D1 (CCND1).	[46]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[47]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[48]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[49]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of G1/S-specific cyclin-D1 (CCND1).	[50]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[51]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[52]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[53]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[54]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[55]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of G1/S-specific cyclin-D1 (CCND1).	[56]
Lindane	DMB8CNL	Approved	Lindane increases the expression of G1/S-specific cyclin-D1 (CCND1).	[27]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[57]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[58]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of G1/S-specific cyclin-D1 (CCND1).	[59]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[60]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[61]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[62]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[44]
Fluoxetine	DM3PD2C	Approved	Fluoxetine decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[63]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[64]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[65]
Lovastatin	DM9OZWQ	Approved	Lovastatin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[66]
Propofol	DMB4OLE	Approved	Propofol increases the expression of G1/S-specific cyclin-D1 (CCND1).	[67]
Melatonin	DMKWFBT	Approved	Melatonin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[68]
Vitamin A	DMJ2AH4	Approved	Vitamin A decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[69]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of G1/S-specific cyclin-D1 (CCND1).	[70]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of G1/S-specific cyclin-D1 (CCND1).	[71]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of G1/S-specific cyclin-D1 (CCND1).	[35]
Tofacitinib	DMBS370	Approved	Tofacitinib increases the expression of G1/S-specific cyclin-D1 (CCND1).	[72]
Hesperetin	DMKER83	Approved	Hesperetin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[73]
Thioridazine	DM35M8J	Approved	Thioridazine decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[74]
Lapatinib	DM3BH1Y	Approved	Lapatinib decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[75]
Benzoic acid	DMKB9FI	Approved	Benzoic acid decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[76]
Amodiaquine	DME4RA8	Approved	Amodiaquine affects the expression of G1/S-specific cyclin-D1 (CCND1).	[77]
Masoprocol	DMMVNZ0	Approved	Masoprocol decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[78]
LY2835219	DM93VBZ	Approved	LY2835219 affects the expression of G1/S-specific cyclin-D1 (CCND1).	[79]
Ethacrynic acid	DM60QMR	Approved	Ethacrynic acid decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[80]
Reserpine	DM6VM38	Approved	Reserpine decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[81]
Vemurafenib	DM62UG5	Approved	Vemurafenib decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[82]
Promegestone	DMK4S8I	Approved	Promegestone increases the expression of G1/S-specific cyclin-D1 (CCND1).	[83]
Digitoxin	DMWVIGP	Approved	Digitoxin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[84]
Dronedarone	DMA8FS5	Approved	Dronedarone decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[85]
Cotinine	DMCEZ1B	Approved	Cotinine increases the expression of G1/S-specific cyclin-D1 (CCND1).	[86]
Dutasteride	DMQ4TJK	Approved	Dutasteride increases the expression of G1/S-specific cyclin-D1 (CCND1).	[87]
Letrozole	DMH07Y3	Approved	Letrozole decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[88]
Furazolidone	DM3P6V7	Approved	Furazolidone increases the expression of G1/S-specific cyclin-D1 (CCND1).	[89]
Acitretin	DM8BKU9	Approved	Acitretin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[90]
Regorafenib	DMHSY1I	Approved	Regorafenib decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[91]
Tetracaine	DM9J6C2	Approved	Tetracaine decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[92]
SR141716A	DMCO5JZ	Approved	SR141716A decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[93]
Momelotinib	DMF98Q0	Approved	Momelotinib decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[94]
Hesperidin	DMI5DW1	Approved	Hesperidin decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[95]
Hexachlorophene	DMLKSE0	Approved	Hexachlorophene decreases the expression of G1/S-specific cyclin-D1 (CCND1).	[96]

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