Target Information

Target General Infomation
Target ID
T12355
Former ID
TTDR00397
Target Name
G1/S-specific cyclin D1
Gene Name
CCND1
Synonyms
BCL-1 oncogene; Cyclin D1; PRAD1 oncogene; CCND1
Target Type
Clinical Trial
Disease Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
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 substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependentmanner 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.
Target Validation
T12355
UniProt ID
P24385
Sequence
MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETCAPSVSYFKCVQKEVLPSMRKIV
ATWMLEVCEEQKCEEEVFPLAMNYLDRFLSLEPVKKSRLQLLGATCMFVASKMKETIPLT
AEKLCIYTDNSIRPEELLQMELLLVNKLKWNLAAMTPHDFIEHFLSKMPEAEENKQIIRK
HAQTFVALCATDVKFISNPPSMVAAGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCD
PDCLRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDLACTPTDVRDVDI
Drugs and Mode of Action
Drug(s) Briciclib Drug Info Phase 1 Solid tumours [1]
Inhibitor 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione Drug Info [2]
3,4-diphenyl-1H-pyrrole-2,5-dione Drug Info [2]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione Drug Info [2]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione Drug Info [2]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Drug Info [3]
7-hydroxycoumarin Drug Info [4]
Briciclib Drug Info [5]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
DRM DRM Info
Pathways
KEGG Pathway FoxO signaling pathway
Cell cycle
p53 signaling pathway
PI3K-Akt signaling pathway
AMPK signaling pathway
Wnt signaling pathway
Hippo signaling pathway
Focal adhesion
Jak-STAT signaling pathway
Prolactin signaling pathway
Thyroid hormone signaling pathway
Oxytocin signaling pathway
Hepatitis B
Measles
HTLV-I infection
Pathways in cancer
Viral carcinogenesis
Proteoglycans in cancer
MicroRNAs in cancer
Colorectal cancer
Pancreatic cancer
Endometrial cancer
Glioma
Prostate cancer
Thyroid cancer
Melanoma
Bladder cancer
Chronic myeloid leukemia
Acute myeloid leukemia
Small cell lung cancer
Non-small cell lung cancer
Viral myocarditis
NetPath Pathway TCR Signaling Pathway
IL2 Signaling Pathway
EGFR1 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
Notch Signaling Pathway
Wnt Signaling Pathway
PANTHER Pathway PI3 kinase pathway
Wnt signaling pathway
CCKR signaling map ST
Pathway Interaction Database Notch signaling pathway
Coregulation of Androgen receptor activity
Validated transcriptional targets of AP1 family members Fra1 and Fra2
Presenilin action in Notch and Wnt signaling
Integrin-linked kinase signaling
Regulation of Telomerase
E-cadherin signaling in the nascent adherens junction
ATF-2 transcription factor network
AP-1 transcription factor network
FOXM1 transcription factor network
Neurotrophic factor-mediated Trk receptor signaling
C-MYB transcription factor network
Validated nuclear estrogen receptor alpha network
Signaling mediated by p38-gamma and p38-delta
Regulation of nuclear beta catenin signaling and target gene transcription
Validated targets of C-MYC transcriptional repression
Trk receptor signaling mediated by PI3K and PLC-gamma
Regulation of retinoblastoma protein
Signaling events mediated by focal adhesion kinase
Reactome Pre-NOTCH Transcription and Translation
RMTs methylate histone arginines
Ubiquitin-dependent degradation of Cyclin D1
Cyclin D associated events in G1
WikiPathways DNA Damage Response (only ATM dependent)
DNA Damage Response
Notch Signaling Pathway
G1 to S cell cycle control
Wnt Signaling Pathway and Pluripotency
TGF beta Signaling Pathway
Wnt Signaling Pathway Netpath
Copper homeostasis
Focal Adhesion
PPAR Alpha Pathway
Mesodermal Commitment Pathway
Organogenesis (Part 2 of 3)
Bladder Cancer
Pre-NOTCH Expression and Processing
S Phase
Polycystic Kidney Disease Pathway
Retinoblastoma (RB) in Cancer
Spinal Cord Injury
Integrated Pancreatic Cancer Pathway
Prostate Cancer
Signaling Pathways in Glioblastoma
IL-7 Signaling Pathway
Leptin signaling pathway
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in epithelium - TarBase
Integrated Breast Cancer Pathway
miRNAs involved in DNA damage response
miRNA Regulation of DNA Damage Response
Androgen receptor signaling pathway
References
REF 1ClinicalTrials.gov (NCT02168725) Dose-escalation, Safety and Pharmacokinetic Study of Briciclib in Advanced Solid Tumors. U.S. National Institutes of Health.
REF 2J Med Chem. 2006 Feb 23;49(4):1271-81.Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors.
REF 3J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects.
REF 4Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin. Lung Cancer. 2001 Nov;34(2):185-94.
REF 5Clinical pipeline report, company report or official report of Onconova.

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