Target Information
| Target General Information | Top | |||||
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| Target ID |
T12355
(Former ID: TTDR00397)
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| Target Name |
G1/S-specific cyclin-D1 (CCND1)
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| Synonyms |
PRAD1 oncogene; PRAD1; Cyclin D1; BCL1; BCL-1 oncogene; BCL-1; B-cell lymphoma 1 protein
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| Gene Name |
CCND1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Myeloproliferative neoplasm [ICD-11: 2A20] | |||||
| Function |
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-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. 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.
Click to Show/Hide
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| UniProt ID | ||||||
| Sequence |
MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETCAPSVSYFKCVQKEVLPSMRKIV
ATWMLEVCEEQKCEEEVFPLAMNYLDRFLSLEPVKKSRLQLLGATCMFVASKMKETIPLT AEKLCIYTDNSIRPEELLQMELLLVNKLKWNLAAMTPHDFIEHFLSKMPEAEENKQIIRK HAQTFVALCATDVKFISNPPSMVAAGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCD PDCLRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDLACTPTDVRDVDI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A05675 | |||||
| HIT2.0 ID | T93WZG | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | ABT-263 | Drug Info | Phase 3 | Myelofibrosis | [2] | |
| 2 | Briciclib | Drug Info | Phase 1 | Solid tumour/cancer | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 8 Inhibitor drugs | + | ||||
| 1 | ABT-263 | Drug Info | [1] | |||
| 2 | Briciclib | Drug Info | [4] | |||
| 3 | 3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione | Drug Info | [5] | |||
| 4 | 3,4-diphenyl-1H-pyrrole-2,5-dione | Drug Info | [5] | |||
| 5 | 3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione | Drug Info | [5] | |||
| 6 | 3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione | Drug Info | [5] | |||
| 7 | 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol | Drug Info | [6] | |||
| 8 | 7-hydroxycoumarin | Drug Info | [7] | |||
| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Drug Resistance Mutation (DRM) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 2 | ClinicalTrials.gov (NCT04472598) Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis (TRANSFORM-1). U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT02168725) Dose-escalation, Safety and Pharmacokinetic Study of Briciclib in Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 4 | Clinical pipeline report, company report or official report of Onconova. | |||||
| REF 5 | Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81. | |||||
| REF 6 | 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9. | |||||
| REF 7 | Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin. Lung Cancer. 2001 Nov;34(2):185-94. | |||||
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